Immunomodulators: types, application features and contraindications

Questions:

• What is an immunomodulator?
• Immunostimulants and immunomodulators: differences
• Classification
• Action and use of immunomodulators and immunostimulants
• For children
• For children under one year old
• During pregnancy
• Natural immunomodulators
• For a cold
• Harm and contraindications
• Is an immunogram necessary before and after treatment?

Medical specialists answer frequently asked questions from users

Immunostimulants and immunomodulators: differences

Immunostimulants and immunomodulators are two groups of drugs that stimulate the immune system. In a broad sense, these drugs are identical, since they perform the same function, but still, they have differences from each other. In order to once and for all understand and remember what the differences are between immunostimulants and immunomodulators, you need to know what each of these terms means.

Immunomodulators are (conditionally) “weakly neutral” drugs that simply act on the body and force its own immunity to work more thoroughly under certain conditions (for example, during ARVI).

Immunostimulants are more “powerful” and “strong” drugs that are used only in cases where the human immune system suffers significantly, and one’s own immunity cannot cope with even minor diseases. In other words, these drugs are used mainly only for immunodeficiency conditions (for example, HIV).

to the begining

Indications for use

Preparations of immunostimulants and immunomodulators are used for diseases associated with reduced immunity: in immunodeficiency conditions (congenital immunodeficiencies, HIV infection and AIDS, during treatment with immunosuppressants, antitumor drugs, after radiation therapy of malignant tumors), chronic sluggish infections of the respiratory and urinary tract.

The use of immunostimulants is especially indicated in patients who have suffered acute colds with incomplete recovery (bronchitis, tracheitis, laryngitis), as well as in frequently ill individuals in the autumn-winter period.

Interferon preparations are used to treat viral hepatitis C and B, human papillomavirus infection, herpes virus infection, in the treatment and prevention of influenza and colds, multiple sclerosis, and cancer.

Glatiramer acetate is used in the treatment of multiple sclerosis.

Levamisole is also prescribed for the treatment of helminthic infestations - helminthiases caused by roundworms (roundworms, pinworms).

Classification

• 1. Thymic - increase the number of special cells (T cells), which largely determine the adequacy of the immune response. The latest generations of thymic drugs are synthetic analogues of thymus hormones, or the human thymus gland.
• 2. Bone marrow - they contain the so-called. myelopeptides, which have both a stimulating effect on T cells and an inhibitory effect on malignant tumor cells.
• 3. Microbial. They combine two actions – vaccinating (specific) and non-specific.
• 4. Cytokines are endogenous immunoregulatory molecules, the deficiency of which does not allow the body to adequately respond to the viral threat.
• 5. Nucleic acids.
• 6. Chemically pure immunomodulators with a wide spectrum of action - immune stimulation, antioxidant, antitoxic. They are also capable of providing a membrane-protective effect.

to the begining

Publications in the media

Immunomodulators are drugs that eliminate imbalances in various parts of the immune system. In this article we will look at the different types of drugs in this group.

In addition to somatic and infectious diseases, which are widespread among people, the human body is adversely affected by social (poor nutrition, housing conditions) and environmental factors, medical measures (surgical interventions, etc.), in which the immune system primarily suffers, and secondary immunodeficiencies. Despite the constant improvement of basic treatment methods for this group of diseases, the effectiveness of treatment remains at a fairly low level.

Research conducted in many countries around the world has made it possible to develop and introduce into clinical practice new integrated approaches to the treatment and prevention of various nosological forms of diseases, taking into account the degree of disturbances in the immune system. An important aspect in preventing relapses and treating diseases, as well as in preventing immunodeficiencies, is the combination of basic therapy with the use of immunomodulators. The action of these drugs should be aimed at immunocorrection, i.e. to reduce high and increase low indicators.

Depending on their origin, immunomodulators are divided into 6 main groups: microbial, thymic, bone marrow, cytokines, nucleic acids and chemically pure immunomodulators.

Microbial immunomodulators

Immunomodulators of microbial origin can be roughly divided into 3 generations. The first drug approved for medical use as an immunostimulant was the BCG vaccine, which has a pronounced ability to enhance factors of both innate and acquired immunity. First generation microbial preparations also include Pyrogenal and prodigiosan, which are polysaccharides of bacterial origin. Currently, due to pyrogenicity and other side effects, they are rarely used.

Microbial preparations of the second generation, in turn, include lysates (Bronchomunal, IPC-19, Imudon, Broncho-Vaxom) and ribosomes (Ribomunil) of bacteria related mainly to pathogens of respiratory infections (Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influezae, etc.). These drugs have a dual purpose - specific (vaccinating) and nonspecific (immunostimulating).

Finally, Lykopid can be classified as a microbial preparation of the third generation. It consists of a natural disaccharide - glucosaminylmuramyl and a synthetic dipeptide attached to it - L-alanyl-D-isoglutamine. In the body, the main target for microbial immunomodulators are phagocytic cells. Under the influence of these drugs, the functional properties of phagocytes are enhanced (phagocytosis and intracellular killing of absorbed bacteria are increased), and the production of proinflammatory cytokines necessary for the initiation of humoral and cellular immunity increases. As a result, antibody production may increase and the formation of antigen-specific T-helper and T-killer cells may be activated.

Thymic immunomodulators

The ancestor of the first generation thymic drugs in Russia was Taktivin, a complex of peptides isolated from the thymus gland of cattle. Preparations containing a complex of thymic peptides also include Timalin, Timoptin, etc., and those containing thymus extracts include Timostimulin and Vilozen. The clinical effectiveness of first generation thymic drugs is beyond doubt, but they have a drawback - they are an unseparated mixture of bioactive peptides that are difficult to standardize. Progress in the field of drugs of thymic origin proceeded through the creation of drugs of the second and third generations - synthetic analogues of natural thymic hormones or fragments of these hormones that have bioactivity. The last direction turned out to be the most productive. Based on one of the fragments, including amino acid residues of the active center of thymopoietin, the synthetic hexapeptide Immunofan was created. Naturally, in accordance with the name, the main target for immunomodulators of thymic origin are T-lymphocytes. With initially low levels, drugs of this series increase the number of T cells and their functional activity. The pharmacological effect of the synthetic thymic dipeptide Thymogen is to increase the level of cyclic nucleotides by analogy with the effect of the thymic hormone thymopoietin.

Immunomodulators obtained from the bone marrow of mammals (pigs or calves) include Myelopid. It contains 6 bone marrow-specific immune response mediators called myelopeptides (MPs), which have the ability to stimulate various parts of the immune response, especially humoral immunity. Each MP has a specific biological effect, the combination of which determines its clinical effect. MP-1 restores the normal balance of activity of T-helpers and T-suppressors. MP-2 suppresses the proliferation of malignant cells and significantly reduces the ability of tumor cells to produce toxic substances that inhibit the functional activity of T-lymphocytes. MP-3 stimulates the activity of the phagocytic component of immunity and, therefore, increases anti-infective immunity. MP-4 affects the differentiation of hematopoietic cells, promoting their faster maturation, i.e., it has a leukopoietic effect. In immunodeficiency states, the drug restores the indicators of the B- and T-immune systems, stimulates the production of antibodies and the functional activity of immunocompetent cells, and helps restore a number of other indicators of the humoral immunity.

Other groups of immunomodulators

The regulation of the developed immune response is carried out by cytokines - a complex complex of endogenous immunoregulatory molecules, which are still the basis for the creation of a large group of both natural and recombinant immunomodulators. The first group includes Leukinferon and Superlymph, the second group includes Beta-leukin, Roncoleukin and Leukomax (molgramostim).

The group of chemically pure immunomodulators can be divided into 2 subgroups - low molecular weight and high molecular weight. The first include drugs that additionally have immunotropic activity. Their ancestor was levamisole (Dekaris), a well-known anthelmintic agent, which was subsequently found to have pronounced immunostimulating properties. Another promising drug from the subgroup of low-molecular immunomodulators is Galavit, a phthalhydrazide derivative. The peculiarity of this drug is the presence of not only immunomodulatory, but also pronounced anti-inflammatory properties. The subgroup of low-molecular immunomodulators also includes 3 synthetic oligopeptides: Gepon, Glutoxim and Alloferon.

High-molecular chemically pure immunomodulators obtained using directed chemical synthesis include Polyoxidonium. This drug is characterized by a wide range of pharmacological effects on the body, including immunomodulatory, antioxidant, detoxifying and membrane protective effects.

A wide range of positive effects on the body is also characteristic of immunomodulatory drugs from the group of nucleic acids, which are divided into synthetic (Poludan) and natural (Derinat, sodium nucleinate). In particular, Derinat, which activates antiviral, antifungal and antimicrobial local immunity due to immunomodulatory effects at the cellular and humoral levels and increased phagocytosis, also realizes radioprotective, reparative, anti-inflammatory, analgesic and antitumor and mild anticoagulant effects. This determines the use of this immunomodulator for a very wide range of diseases (primarily infectious) of various nature and localization.

Drugs characterized by pronounced immunomodulatory properties also include interferons and interferon inducers. Interferons, as a component of the body's general cytokine network, are immunoregulatory molecules that affect all cells of the immune system.

Clinical Application

The most justified use of immunomodulators seems to be in cases of immunodeficiency, manifested by an increased infectious morbidity. The main target of these drugs remains secondary immunodeficiencies, which are manifested by frequent recurrent, difficult-to-treat infectious and inflammatory diseases of all localizations and any etiology. Each chronic infectious-inflammatory process is based on changes in the immune system, which are one of the reasons for the persistence of this process. Studying the parameters of the immune system may not always reveal these changes. Therefore, in the presence of a chronic infectious-inflammatory process, immunomodulators can be prescribed even if an immunodiagnostic study does not reveal significant deviations in the immune status.

As a rule, in such processes, depending on the type of pathogen, the doctor prescribes antibiotics, antifungals, antivirals or other chemotherapeutic drugs. According to experts, in all cases when antimicrobial agents are used for phenomena of secondary immunological deficiency, it is advisable to prescribe immunomodulators.

In accordance with the basic requirements for immunotropic drugs, they must meet the following characteristics: • have immunomodulatory properties; • have a natural origin, high efficiency; • be safe, have no contraindications, do not cause addiction, adverse reactions and carcinogenic effects; • do not cause immunopathological reactions; • do not provoke excessive sensitization and do not potentiate it in other drugs; • easily metabolized and excreted from the body; • do not interact with other drugs, have high compatibility with them; • have non-parenteral routes of administration.

Currently, the basic principles of immunotherapy have been developed and approved: 1. mandatory determination of immune status before the start of immunotherapy; 2. determination of the level and extent of damage to the immune system; 3. monitoring the dynamics of immune status during immunotherapy; 4. use of immunomodulators only in the presence of characteristic clinical signs and changes in immune status indicators 5. prescription of immunomodulators for preventive purposes to maintain immune status (oncology, surgical interventions, stress, and other influences).

Determining the degree of damage to the immune system is one of the most important stages in selecting a drug for immunomodulatory therapy. The point of application of the drug's action must correspond to the degree of disruption of the activity of a certain part of the immune system in order to ensure maximum effectiveness of the therapy.

Action and use of immunomodulators and immunostimulants

Such drugs are prescribed as part of complex therapy. This is due to the fact that they do not have a direct effect on the pathogen. The immunomodulator corrects and stimulates the body's defense reactions, allowing you to effectively fight infection. But in some cases, the immune system begins to fight against the body's cells (autoimmune diseases) - in this case, immunosuppressants that suppress the immune system are indicated. Suppressors are also used in transplantology to prevent rejection of transplanted donor organs.

The use of immunocorrectors is indicated for a variety of infections (especially chronic, sexually transmitted infections), allergic diseases, neoplasms, and HIV. As a separate (independent) drug, they can be used as a prophylactic agent during epidemics (influenza, ARVI) - for this purpose, both herbal immunomodulators and synthetic complexes can be used. Of the modern and proven immunostimulants, there is o - a unique drug that allows its use starting from 6 months of age. The dosage of the drug is prescribed by the doctor, in accordance with the age and severity of the condition.

to the begining

Immunotherapy: mechanism of action and clinical use of immunocorrective drugs

The number of chronic inflammatory, allergic, autoimmune, endocrine, oncological and other diseases is steadily increasing. Data from epidemiological and statistical studies in recent years indicate a significant deterioration in the nation's health. The experience of world practice in immunoprophylaxis shows that this category of people primarily needs vaccination against infectious diseases. There is evidence that, from a clinical point of view, vaccination of people with various health conditions is safe, but the strength of their immune response is lower than that of practically healthy people. To stimulate the formation of post-vaccination immunity in such patients, various immunomodulatory drugs are prescribed.

It should be noted that Russian researchers have the greatest experience in this area, who have shown that with the correct selection of an immunomodulating drug and its administration regimen, it is possible to obtain a rapid and complete immune response to vaccination in individuals suffering from various pathologies.

One of the main goals when prescribing an immunomodulatory drug during preventive vaccination in persons with various health conditions is not only the prevention of an infectious disease, but also the achievement of positive dynamics in the course of the underlying disease. In this case, the doctor needs to make the right choice of an immunocorrective drug, taking into account not only the nosological form of the disease, but also the initial indicators of the immune status.

The human immune system performs an important function of maintaining the constancy of the internal environment of the body, carried out by recognizing and eliminating from the body foreign substances of an antigenic nature, both endogenously arising (cells modified by viruses, xenobiotics, malignant cells, etc.) and exogenously penetrating ( primarily microbes). This function of the immune system is carried out with the help of factors of innate and acquired (or adaptive) immunity. The first include neutrophils, monocytes, macrophages, dendritic cells, NK and NKT lymphocytes; the second includes T and B cells, which are responsible for the cellular and humoral response, respectively. When the number and functional activity of immune system cells is disrupted, immunological disorders develop: immunodeficiencies, allergic, autoimmune and proliferative processes.

Modern pathology is characterized by the presence of two interrelated and interdependent processes, namely: an increase in the number of chronic infectious diseases caused by opportunistic or opportunistic microbes and a decrease in the immunological reactivity of the population, observed in almost all developed countries.

It is obvious that it is almost impossible to cope with the increase in infectious diseases using antibiotics alone. The antibiotic suppresses the reproduction of the pathogen, but its final elimination from the body is the result of the activity of immune factors. Moreover, long-term uncontrolled use of antibiotics reduces the body's immunological reactivity. Therefore, against the background of suppressed immunoreactivity, the effectiveness of antibiotics, as well as antifungal, antiviral and other chemotherapeutic agents, decreases.

In this regard, doctors' interest in drugs that act on the body's immune system has now sharply increased. The market offers a large number of medicines, food supplements and simply food products that act on the immune system. It is often difficult for a practicing doctor to understand this huge flow of information and proposals and choose the right remedy. In addition, there is currently a lot of confusion in the definitions of what an immunocorrector, an immunomodulator, an immunostimulant is.

The administration of drugs of a chemical or biological nature that have immunotropic activity for therapeutic or prophylactic purposes in diseases associated with immune disorders (the therapeutic effect is associated with their preferential or selective effect on the human immune system) is called immunotherapy, and the drugs themselves can be divided into four large groups:

• immunomodulators;
• immunocorrectors;
• immunostimulants;
• immunosuppressants.

Immunomodulators are drugs with immunotropic activity that, in therapeutic doses, restore the functions of the immune system (effective immune defense).

Immunocorrectors are means and effects (including medicinal ones) that have immunotropism, which normalize a specific disturbed part of the immune system (components or subcomponents of T-cell immunity, B-cell immunity, phagocytosis, complement). Thus, immunocorrectors are immunomodulators of “point” action.

Immunostimulants are drugs that enhance the immune response (medicines, nutritional supplements, adjuvants and other agents of biological or chemical nature that stimulate immune processes).

Immunosuppressants are drugs that suppress the immune response (drugs that have immunotropic or nonspecific effects, and various other agents of biological or chemical nature that suppress immune processes).

In order for a particular drug to be classified as an immunomodulator, its ability to change the body’s immunological reactivity must be proven depending on its initial state, i.e., the ability to increase or decrease, respectively, decreased or increased immunity levels. To do this, the drug under investigation must undergo preclinical trials conducted in accordance with the Methodological Recommendations approved by the State Pharmacological Committee under the Ministry of Health of the Russian Federation dated December 10, 1998. As a result of these tests, its immunomodulatory effect on the components of the immune system must be proven: phagocytosis, complement system, humoral immunity, cellular immunity, cytokine system. Next, the investigational drug must undergo clinical trials in accordance with GCP rules, as a result of which its clinical and immunological effectiveness will be proven based on a double-blind randomized study. Ultimately, the drug is registered by the Federal State Committee of the Russian Ministry of Health as an immunomodulator and permission is issued for its widespread medical use and industrial production.

Only the drug that has passed preclinical and clinical trials according to the rules described above meets the requirements for immunomodulatory drugs.

When analyzing the pharmacological action of immunomodulators, it is necessary to take into account the amazing feature of the functioning of the immune system, which “works” like communicating vessels, i.e. the presence of a load on one “bowl” sets the entire system in motion. In this regard, regardless of the initial direction, under the influence of the immunomodulator, the functional activity of the entire immune system as a whole ultimately changes to one degree or another. An immunomodulator can have a selective effect on the corresponding component of the immune system, but the final effect of its impact on the immune system will always be multifaceted. For example, substance X induces the formation of only one interleukin-2 (IL-2). But this cytokine enhances the proliferation of T, B and NK cells, increases the functional activity of macrophages, NK cells, cytotoxic lymphocytes (CTL), etc. IL-2 is no exception in this regard. All cytokines are the main regulators of immunity, mediating the effect on the immune system of both specific and nonspecific stimuli, and have multiple and diverse effects on the immune system. Currently, no cytokines with strictly specific activity have been identified. Such features of the functioning of the immune system make it almost impossible for an immunomodulator to exist with an absolutely selective final effect on the immune system. This position allows us to formulate the following principle.

Any immunomodulator that selectively acts on the corresponding component of immunity (phagocytosis, cellular or humoral immunity) will, to one degree or another, affect all other components of the immune system.

There are three main groups of immune system diseases: immunodeficiencies, allergic and autoimmune processes. Let's consider for which diseases it is advisable to use immunomodulators.

Allergic diseases. For allergic diseases, the use of immunomodulators is advisable in cases where these diseases are complicated by any manifestations of secondary immune deficiency: for example, atopic dermatitis with pyoderma, bronchial asthma with symptoms of chronic purulent-obstructive bronchitis, recurrent herpetic or cytomegalovirus infection, etc. In these cases, the effect of immunomodulators is aimed at eliminating the infectious focus in a patient with an allergic process. In some cases, this can significantly improve the clinical picture of the underlying disease. For example, the use of immunomodulatory therapy in patients with bronchial asthma can extend the duration of remission to one year. However, in all these cases, immunomodulatory therapy is not aimed at the main cause of the disease, i.e., it is not etiotropic. As is known, in allergic diseases, Th2 cells are activated and the production of cytokines IL-4, IL-5, IL-13 is increased. IL-5 promotes eosinophil maturation and activation. IL-4 and IL-13 induce B cells to synthesize immunoglobulin IgE. Consequently, from an immunological point of view, increased activity of Th2 cells is the main link in the pathogenesis of allergic reactions. From here it becomes obvious that one of the directions in the immunomodulatory therapy of these processes is the use of drugs that reduce the activity of Th2 cells and increase the activity of Th1 cells, i.e. immunomodulators.

Autoimmune diseases. For autoimmune diseases, immunotropic drugs belonging to the group of immunosuppressants, the action of which is aimed at suppressing the autoimmune inflammatory process, are currently widely used. Their use, as a rule, gives a quick and good clinical effect. However, such treatment probably cannot be considered etiotropic, since it is aimed at the pathogenesis, and not at the cause of the disease. Thus, the use of hormonal drugs for multiple sclerosis, which is a Thl-mediated disease, gives a good clinical effect, but does not prolong the duration of remission - an important indicator of the effectiveness of therapy. The etiopathogenesis of many autoimmune diseases, as in allergic processes, is based on a Th1/Th2 imbalance. With multiple sclerosis, rheumatoid arthritis, autoimmune thyroiditis, increased activity of Th1 cells is observed, with systemic lupus erythematosus, autoimmune vasculitis, and some types of anemia - Th2 cells. The basis for the use of immunomodulators in autoimmune processes, as well as in allergies, are infectious processes that complicate the course of the underlying disease.

Immunodeficiencies. Increased infectious morbidity is the main manifestation of both primary and secondary immunodeficiencies. The question arises: is it advisable to use immunomodulatory drugs for primary immunodeficiencies, which are based on a genetic defect. Naturally, it is impossible to correct a genetic defect with the help of these drugs. But anti-infective protection is multicomponent, and it can be expected that with some increase in the functional activity of a normally functioning component of the immune system using immunomodulators, the “poor performance” of the defective component will be compensated, at least partially. A significant improvement in the clinical condition and indicators of immune status is observed in patients with reduced levels of all classes of immunoglobulins (general variable immunological deficiency) when treated with immunomodulatory drugs that activate phagocytosis, in particular Polyoxidonium. Well-thought-out use of immunomodulatory therapy in patients with some forms of primary immunodeficiencies can lead to good clinical results.

The main target for the use of immunomodulatory drugs is secondary immunodeficiencies, which are characterized by frequent, recurrent, difficult-to-treat infectious and inflammatory processes of all localizations and any etiology. Any chronic infectious-inflammatory process is based on certain changes in the immune system, which serve as one of the reasons for the existence of this process. A study of the parameters of the immune system may not always reveal these changes, therefore, if there is a chronic infectious-inflammatory process in the body, the patient can be prescribed immunomodulatory drugs even if the immunodiagnostic study does not reveal significant deviations in the immune status. As a rule, in these processes, depending on the type of pathogen, the doctor prescribes antibiotics, antifungals, antivirals or other chemotherapeutic drugs. We believe that in all cases when a doctor prescribes antimicrobial agents for symptoms of secondary immunological deficiency, immunomodulatory therapy should also be prescribed. When treating processes, immunomodulators are used mainly in complex treatment together with etiotropic chemotherapeutic agents.

Thus, the main criterion for prescribing an immunomodulator is the clinical picture of the disease, manifested by the presence of a chronic infectious-inflammatory process that is difficult to adequately respond to anti-infectious treatment.

The question arises: how to use immunomodulators in the complex treatment of chronic infections. We believe that immunomodulators should be prescribed not after or before taking antibiotics or antiviral drugs, but simultaneously with them. In this case, the pathogen will be dealt a double blow: an antibiotic or other chemotherapeutic agent reduces the functional activity of the microbe, and the immunomodulator increases the functional activity of the cells of the immune system, thereby achieving more effective elimination of the pathogen from the body. The “fashionable” statement about the negative impact of antibiotics on the immune system should be avoided. Currently, doctors have a number of antibiotics that do not have an inhibitory effect on the immune system. All other things being equal, the doctor should give preference to the latter. A separate issue is the use of immunomodulators for acute bacterial and viral infections.

As a rule, their use is not recommended for acute processes, since this can aggravate their course. For example, during a viral infection, activation of CTLs can cause a fatal outcome due to massive destruction of tissues infected by the virus. This should probably be kept in mind when prescribing chemicals, as well as drugs of bacterial origin, which are powerful inducers of pro-inflammatory cytokines. The use of immunomodulators in acute infectious processes, especially of the bronchopulmonary apparatus, may be justified in immunologically compromised people, for example, in people who are often and long-term ill. In these cases, immunomodulators are used to prevent the development of post-infectious complications. The presence of detoxifying and antioxidant properties in Polyoxidonium makes it possible to use it in acute infectious diseases. Clinical practice shows the effectiveness and safety of its use in acute infections. We believe that not only Polyoxidonium, but also other immunomodulators with antioxidant and detoxifying properties can be used in acute infectious processes in immunologically compromised individuals.

The question often arises whether immunomodulation can be performed as monotherapy. R.?V.?Petrov was the first to formulate the concept of “immunorehabilitation”, which is understood as a complex of medicinal and non-medicinal therapeutic measures aimed at restoring the functional activity of the immune system and human health. We believe that during immunorehabilitation measures, immunomodulators can be used as monotherapy and in combination with various restorative agents. This is justified:

• in people with incomplete recovery (presence of bronchitis, laryngitis, tracheitis, etc.) after suffering an acute infectious disease;
• in people who are often and long-term ill before the start of the autumn-winter season, especially in environmentally unfavorable regions;
• in cancer patients to improve quality of life.

In conclusion, we can formulate some general principles for the use of immunomodulators in patients with insufficient anti-infective protection:

• Immunomodulators are prescribed in complex therapy simultaneously with antibiotics, antifungals, antiprotozoals or antivirals.
• It is advisable to early prescribe immunomodulators from the first day of using a chemotherapeutic etiotropic agent.
• Immunomodulators acting on the phagocytic component of immunity can be prescribed to patients with both identified and unidentified disorders of the immune status, i.e., the basis for prescribing the drug is the presence of clinical markers of immunodeficiency.
• If a given medical institution has the appropriate material and technical base, it is advisable to use immunomodulators against the background of immunological monitoring. This monitoring should be carried out regardless of whether initial changes in the immune system are detected or not.
• Immunomodulators can be used as monotherapy when carrying out immunorehabilitation measures, in particular, in case of incomplete recovery after an acute infectious disease.
• A decrease in any parameter of immunity detected during an immunodiagnostic study in a practically healthy person is not necessarily a basis for prescribing immunomodulatory therapy.

Use of immunomodulators in clinical practice

In recent years, Ribomunil, a ribosomal immunomodulator of bacterial origin, has been successfully used. The clinical effectiveness of Ribomunil is due to its complex immunomodulatory effect. Ribomunil contains ribosomal fractions of Streptococcus pneumoniae, S. pyogenes, Haemophilus influenzae, Klebsiella pneumoniae, as well as K. pneumoniae cell wall proteoglycans. The analysis of the effectiveness of including Ribomunil in the complex of rehabilitation measures for frequently ill children indicates that the rate of their recovery was significantly ahead of the similar indicators of the comparison group [8, 9, 10]. It was found that the effect of ribosomal immunization appeared already in the first three months of therapy and subsequently persisted for another 18 months.

At the same time, the frequency of acute respiratory infections during the monitoring period generally decreased by 43.3–53.8%. It should be especially emphasized that, thanks to a decrease in respiratory morbidity, the number of temporary medical exemptions from vaccination within the prescribed periods was significantly reduced. In the observed organized children's groups, this made it possible to achieve a regulated level of vaccination coverage. In addition, it was found that the use of Ribomunil not only prevents the development of respiratory infections, but also significantly affects the effectiveness of vaccination. It was noted that a significant increase in the preventive effectiveness of influenza vaccination in frequently ill children can be achieved if they are vaccinated while taking Ribomunil. Similar results were obtained by V.?F.?Uchaikin et al. (2000) during influenza vaccination in children with various health conditions [10, 11]. The authors showed that in children vaccinated against influenza and simultaneously receiving Ribomunil, the total incidence of influenza and other acute respiratory viral infections was 2.5 times lower than in the group where only active specific immunization was used.

Currently, there are positive results from the use of a drug such as Imunofan as a means of immunorehabilitation. The choice of the drug is due to the fact that Imunofan has virtually no effect on the production of reagin antibodies of the IgE class and thereby does not enhance immediate hypersensitivity reactions. Moreover, in individuals with an initially high level of antibodies of this class (bronchial asthma, atopic dermatitis, hay fever, angioedema), the use of Imunofan led to a decrease in the concentration of IgE with a decrease in the severity of clinical manifestations of diseases [15, 16]. The instructions for the drug Imunofan, approved by the Pharmacological Committee of the Ministry of Health of Russia, regulate the use of the drug in the vaccine prophylaxis scheme.

T.?P.?Markova and D.?G.?Chuvirov (State Educational Establishment Institute for Advanced Studies "Medbioextrem" of the Ministry of Health of Russia, Moscow) used Imunofan for revaccination against diphtheria of 60 long-term and often ill children with a specific antibody titer of 1:20–1 :40 before the II and IV revaccination with ADS-M [12]. It was found that the combined use of Imunofan during revaccination with ADS-M does not lead to an increase in post-vaccination reactions and increases the effectiveness of vaccination by 1.7–1.8 times, the effect of which persists for a year.

The effect of the use of Myelopid and Polyoxidonium (combined use of Polyoxidonium at a dose of 3–6 mg or Myelopid at a dose of 3 mg intranasally within 5 days from the day of vaccination or intramuscularly on the day of vaccination) was also studied during revaccination against diphtheria in 90 children who did not have a protective titer antibodies against diphtheria, before the second and fourth revaccination. The age of children is from 6 to 14 years [13]. The geometric mean antibody titer in children who received Polyoxidonium or Myelopid intranasally simultaneously with revaccination at various periods of the examination was higher than in the control group revaccinated in the usual way (after 45 days; 6 months; 1 year), the difference was statistically significant. Moreover, in the control group, 5 (14%) children 45 days later and 11 (31.8%) children 1 year after revaccination did not have a protective antibody titer, which was not observed in children receiving immunocorrectors.

With combined intranasal or intramuscular use of Myelopid or Polyoxidonium, an increase in macrophage parameters (phagocytosis, chemiluminescence), the absolute number of CD3+, CD4+ T cells, serum immunoglobulins IgG, IgA was also observed compared to the control group. Similar data were obtained by the authors during revaccination against the background of the use of Myelopid and Polyoxidonium for hepatitis B, measles, rubella, and mumps in frequently ill children [13].

S.?M.?Kharit (Research Institute of Childhood Infections of the Ministry of Health and Social Development of the Russian Federation), E.?P.?Nacharova, S.?V.?Petlenko (Military Medical Academy named after S.?M.?Kirov, St. Petersburg) the effect of the drug Thymogen on the effectiveness and safety of vaccination against measles and mumps was assessed [14]. Children of the first group (16 people), 10 days before vaccination, received intranasally the synthetic peptide immunomodulator Thymogen (0.025% solution of glutamyl-tryptophan in 0.9% NaCl in the form of a metered spray) daily for 5 days at a dose of 25 mcg once a day. The use of the drug was completed 5 days before vaccination.

In children of the second group (16 children), a spray with saline solution containing no active substance was used as a placebo according to the same scheme. Observation in the dynamics of the post-vaccination period showed that in the group receiving placebo, two children (14.3%) had normal vaccine reactions from the 6th to the 9th day in the form of hyperemia of the pharynx, rhinitis, low-grade fever 37.2–37. 5 °C.? One child (7.1%) from this group fell ill with an acute respiratory infection on the 17th day after immunization. In the group vaccinated with preliminary use of Thymogen, all children had an asymptomatic course of the post-vaccination period and not a single child fell ill within a month after vaccination. Not a single child had any unusual or pathological reactions to the vaccine.

A study of antibody titers depending on their level showed that preliminary use of Thymogen led to the fact that already on the 14th day, a protective titer of anti-measles antibodies was determined in 100% of those examined, while in the placebo group 35.7% of individuals had specific antibodies were not determined. Moreover, in 87.5% of children in the first group, titers of specific antibodies were higher than when using placebo. The dynamics of anti-mumps antibodies were similar.

The results obtained allowed the authors to conclude that the divaccine is a low-reactogenic drug, and the administration of Thymogen before immunization contributes to a smoother course of the post-vaccination period and has a pronounced stimulating effect on the intensity of specific antibody formation, promoting the formation of protective antibody titers in all vaccinated individuals by the 14th day and the predominance of high antibody titers in 80–100% of those vaccinated on the 30th day after revaccination.

Interesting data were obtained from the use of topical bacterial lysate IRS 19 and the drug Viferon in frequently ill children before vaccination against measles and mumps. The use of IRS 19 in the pre-vaccination period helped to reduce the degree of antigenic load, prepare children for vaccination, reduce intercurrent diseases and reduce adverse reactions in the post-vaccination period, and create specific immunity at a high protective level. Vaccination against the background of Viferon made it possible to avoid the accumulation of intercurrent diseases and also reduce the number of undesirable post-vaccination reactions, contributed to the rapid formation and slower decrease in the level of antibodies to the measles and mumps virus [17].

The use of immunocorrective drugs in patients with impaired health before vaccination and during the post-vaccination period helps to reduce the accumulation of intercurrent diseases, ensures a “smooth” course of the post-vaccination period, promotes the rapid and intense production of specific antibodies, which ultimately leads to an increase in vaccination coverage within the prescribed period and improving the quality of children's health.

Literature

1. Khaitov R.?M., Pinegin B.?V. Immunomodulators: mechanism of action and clinical application // Immunology. 2003. No. 4, p. 196–203.
2. Khaitov R.?M., Pinegin B.?V. Modern immunomodulators: basic principles of their application // Immunology. 2000. No. 5, p. 4–7.
3. Khaitov R.?M., Pinegin B.?V. Immunomodulators and some aspects of their clinical use // Klin. honey. 1996. T. 74. No. 8, p. 7–12.
4. Mashkovsky M.?D. Drugs that correct immune processes (immunomodulators, immunocorrectors) In the book: Mashkovsky M.?D.?Medicines: (a manual for doctors). M., 1993. Part 2. pp. 192–209.
5. Korovina N.?A. et al. Immunocorrective therapy for frequently and long-term ill children: A guide for doctors. M., 1998.
6. Petrova T.?I., Sakharova A.?S. Brief reference book for an immunologist: Methodological recommendations. Cheboksary, 2002.
7. Kostinov M.?P. Basics of vaccine prevention in children with chronic pathology. M., 2002. 318 p.
8. Korovina N.?A., Zaplatnikov A.?L., Cheburkin A.?V., Zakharova I.?N. Frequently and long-term ill children: modern possibilities of immunorehabilitation. M.: Kontimed, 2001; 68.
9. Zaplatnikov A.?L. Clinical and pathogenetic rationale for immunotherapy and immunoprophylaxis of viral and bacterial diseases in children. Author's abstract. diss... doc. honey. Sci. M., 2003.
10. Experience of using Ribomunil in Russian pediatric practice. Collection of scientific papers. Ed. N.?A.?Korovina. M., 2002.
11. Michel F.?B. Ribomunil. Chester: Adis International Limited, 1996.
12. Markova T.?P., Chuvirov D.?G. Clinical and immunological examination and selection of patients with immune system dysfunctions for forced vaccination, determination of the level of specific antibodies. Allergy, asthma and clinical immunology. M., 2003, vol. 7, no. 9, p. 84–86.
13. Markova T.?P., Kharyanova M.?E. Strengthening post-vaccination immunity in long-term and frequently ill children // Allergy, asthma and clinical immunology, 2001, No. 1.
14. Kharit S.?M., Nacharova E.?P., Petlenko S.?V. The use of thymogen to increase the effectiveness of immunization against measles and mumps in children living in environmentally unfavorable regions // Epidemiology and vaccine prevention, 2005, No. 2, p. 15–21.
15. Lebedev V.?V., Danilina A.?V., Sgibova I.?V. and others. Pharmacological immunorehabilitation in the system of specific immunoprophylaxis and vaccine therapy: modern approaches and development prospects // Int J Immunorehabilitation, 2000; 2 (1): 48–53.
16. Illek Ya.?Yu., Zaitseva G.?A., Leushina N.?P. and others. Imunofan in the complex treatment of children with allergic diathesis // Pediatrics, 1999; 4:71–3.
17. Kostinov M.?P. Immunocorrection of the vaccine process in persons with impaired health. M., 2006, 172 p.

V. P. Afinogenova I. V. Lukachev M. P. Kostinov , Doctor of Medical Sciences, Professor

State Research Institute of Vaccines and Serums named after. I. I. Mechnikova RAMS , Moscow

Contact information for authors for correspondence

For children

It is best to stimulate the immune system in children without taking medications. But still, there are cases when you simply cannot do without immunomodulators, and then the drug of choice becomes “Thymogen”, since this is the only drug made on the basis of substances identical to those produced by the thymus (thymus gland).

In childhood, frequent colds are inevitable, due to the fact that the child’s immune system is still imperfect (it completes its formation by the age of 9-14 years). During this period, the child goes to kindergarten, then school. His circle of contacts increases sharply, and along with this, the number of contacts with viruses also increases. Therefore, after consulting a doctor, it makes sense to use Thymogen spray. It can be used in combination with any other medications, has virtually no contraindications, and taking it once a day will not create any inconvenience for the child.

to the begining

Immunomodulators. Is it worth interfering with immunity?

Immunostimulants seem to many to be a universal solution to the problem of frequent colds and recurrent infections. It would seem that it might be better to take a course of pills and thereby strengthen the immune system! But is everything so simple with these drugs?

Briefly about the immune system

The immune system includes a whole complex of organs with fine and complex regulation of joint activity. The central organs of the immune system are the bone marrow and the thymus gland. This is where the main immune cells, leukocytes, are produced. With the bloodstream, they enter the peripheral immune organs - the spleen, lymph nodes and accumulations of lymphoid tissue in the thickness of the mucous membranes.

The main goal of immunity is to identify and destroy all foreign cells and substances that enter the body and pose a danger to it. These can be poisons, foreign bodies, bacteria, viruses, parasites, altered own cells (for example, tumor cells).

Immunology is the science that deals with the treatment of diseases of the immune system. This is one of the most difficult branches of medicine. The immune system is extremely complex, its functioning based on a delicate balance of many types and subtypes of immune cells. This is associated with the caution of immunologists when prescribing any drug that in one way or another interferes with the functioning of this multicomponent system.

What are immunomodulators?

All drugs that correct the functioning of the immune system are called immunomodulators. The structure and origin of these drugs are different. Based on their direction of action, they are divided into immunostimulants and immunosuppressors.

Immunosuppressants are very specific drugs that are used to suppress the immune system. They are used in transplantology and in the treatment of autoimmune diseases. Immunostimulants have the opposite effect - they increase immunity, which encourages doctors, and people without special education, to use them to “strengthen the protective function.”

How do immunostimulants work?

For most of us, immunostimulants are of the greatest interest, so in the future we will talk mainly about them.

The effect of immunostimulants is associated with their influence on one or more parts of the immune system. Some drugs enhance the production of all leukocytes, others affect differentiation - the transformation of a leukocyte into a cell of narrowly targeted action. Specific immunomodulators increase immune protection against only one pathogen - these are well-known vaccinations.

Immunostimulants also include interferons and interferonogens - stimulators of interferon production in the body. These drugs are used primarily for viral diseases.

When are immunostimulants used?

Immunomodulators are used: for chronic and recurrent infectious diseases that are difficult to respond to traditional treatment, viral diseases, and immunodeficiency.

The last point is worth special attention. Frequent colds are not yet a reason to diagnose yourself with immunodeficiency, and therefore you should not take immunostimulants until an immunologist examines your immune system and confirms your suspicions.

Even doctors who do not have an immunological specialty have a hard time imagining the work of the immune system - it is very complex and subtle, and it is not for nothing that immunology is singled out as a separate specialty. And if so, you and I shouldn’t even try to make immunological diagnoses for ourselves, much less take immunocorrectors on our own.

How can you not use immunostimulants?

1. The main thing is that they should not be taken without a doctor’s prescription. It is advisable that the prescription comes from an immunologist.

2. When treating chronic inflammatory diseases, an immunostimulant should not be the main hope and support. They are prescribed only if the main treatment is confirmed to be ineffective.

3. Immunostimulants are not prescribed only because of frequent colds - it is necessary to study an immunogram (a set of tests to determine the content of individual types and subtypes of immune cells in the blood).

4. Do not prescribe two drugs with the same effect at the same time.

5. Immunostimulants cannot be used without immunogram monitoring. Having prescribed the drug, the immunologist must schedule a second appointment with a control study of the immune system.

Are there any complications when taking immunostimulants?

Taking almost any drug can lead to complications. You can read them in the instructions, which are necessarily included in the box with the medicine. But are all the complications listed there?

The fact is that the immunostimulants most used today (except, perhaps, vaccinations) are still very young - they are no more than 10-15 years old. This means that we cannot yet judge the long-term consequences of using these drugs. But gradually long-term complications begin to appear. For example, in some countries the production of certain immunostimulants is being closed, as it turned out that they increase the risk of developing autoimmune diseases.

Another point: taking immunomodulators can lead to excessive stimulation of the immune system. In this case, after an initial improvement in well-being and normalization of immunogram parameters, a sharp deterioration occurs due to depletion of the immune system. The resulting immunodeficiency is extremely difficult to treat.

What immunostimulants can you take on your own?

Yes, there are also drugs that have an immunostimulating effect that you can take on your own. However, they do not officially belong to the group of immunomodulators, but have a similar, albeit less specific and pronounced effect.

Let's start with vitamins. Any vitamin is a substance of multidirectional action, and almost each of them has one or another beneficial, and most importantly, safe effect on the immune system. In a word, taking multivitamins can be equated to measures to strengthen the immune system. By the way, multivitamins usually contain microelements, the lack of which can also cause insufficient function of the immune system. However, remember that multivitamins are also medications, which means they have contraindications.

Herbal immunostimulants are medications that gently and safely strengthen the immune system.

•Ginseng.

•Eleutherococcus.

•Chinese lemongrass.

•Rose hip.

•Aralia Manchurian.

•Thyme

These herbal remedies are sold in pharmacies. In some cases, you can stock up on them yourself. But in any case, before taking it you should read the instructions to avoid overdose and take into account contraindications.

Some foods also have immune-boosting properties. And here there can be only two restrictions. First, you should not be allergic to them. Secondly, you cannot make your diet exclusively from “immune-stimulating” foods: nutrition must be balanced - this, by the way, is a prerequisite for health and strong immunity.

Foods that strengthen the immune system: garlic, walnuts, almost any fresh fruit (due to the high content of vitamins in them), elderberry, watermelon, cabbage, champignons, wheat germ, almonds, fermented milk products, spinach, tea, broccoli, etc. .

This list can be continued for a very long time. By and large, this also includes meat and fish, vegetable oil, vegetables, bran, and grain products.

If you want to strengthen your immune system, do not forget about the benefits of hardening, physical education, and walks in the fresh air. Get proper rest, giving your body time and strength to recover.

Remember that the best immunostimulant is a healthy lifestyle. This product has never let anyone down!

Head prevention department

clinic No. 1

Linkevich L.A.

For children under one year old

It is necessary for the child to develop his own immunity naturally. Children under one year of age who are breastfed receive immunoglobulins from their mother's milk - and these are “endogenous immunomodulators”. But if, nevertheless, a child under one year of age simply needs immunomodulators, then in this case only a doctor can prescribe the drug.

At this age, all drugs should be used with extreme caution, and immunostimulants are no exception. As a rule, when the baby reaches 6 months of age, the natural protection provided by breast milk ceases. Therefore, the child’s body is not always able to resist viruses. The drug "Thymogen" , being identical to the natural substance that is secreted by the child's thymus gland, gently stimulates children's immunity without causing addiction. Indicated for both acute and chronic pathologies caused by bacteria or viruses.

to the begining

Types of immunostimulants

• Herbal preparations
  . These are immunostimulants based on herbal medicines - echinacea, lemongrass, chicory, clover, lungwort. Without suppressing natural hormones, they restore the body's defenses naturally. Herbal medicines are available in the form of tablets, drops, lozenges, and tinctures. The treatment period is about 2 weeks.
• Immunostimulating drugs of bacterial origin
  . To create drugs of this group, particles of microbial cells – pathogens of respiratory diseases – are used. By themselves, in such small quantities, they cannot cause disease, but they can stimulate the immune system to fight the virus. These medications cope well with infectious respiratory diseases (sore throat, bronchitis, pharyngitis, influenza). Immunostimulants of bacterial origin are produced in the form of granules, drops, tablets. They can be taken from 6 months of age. However, it is contraindicated for use by pregnant and lactating women. And the course of treatment ranges from 2 weeks to one month.
• Medicines of synthetic origin
  . Immunostimulants are based on components obtained in the laboratory. Medicines are prescribed to the patient for the treatment of purulent-inflammatory diseases of the skin, respiratory, and genitourinary systems. Available in the form of spray, creams, solutions, suppositories (rectal suppositories). The course of treatment can last from 10 days to one month.
• Immunostimulants of endogenous origin
  . Drugs that are obtained from the thymus gland and bone marrow. They regulate the production of immune cells, promote the production of antibodies and restore body tissue.

During pregnancy

The use of immunomodulators during pregnancy should be kept to a minimum. During pregnancy, you need to stimulate the immune system with proper nutrition, physical methods, hardening and gymnastics.

The use of medications during pregnancy requires mandatory consultation with a specialist. To correct the protective properties of the expectant mother’s body, you can use multivitamin complexes enhanced with minerals. Naturally, this should be done only as prescribed by a doctor. Homeopathic remedies and herbal stimulants are indicated.

to the begining

Immunostimulants: benefit or harm?

Such drugs should be taken only on the recommendation of a doctor and the dosage of the medication should be strictly observed. Otherwise, the drug will not only not improve the protective mechanisms of the immune system, but on the contrary, it will undermine your immunity. This may manifest itself in an allergic reaction to the drug or its components, the appearance of autoimmune diseases or negative immunological reactions.

Taking immunostimulants in childhood

Some medications can be taken as early as six months of age. Immunostimulants for children are prescribed for frequent colds. This can only be done by an experienced specialist - a pediatrician or immunologist. The doctor will recommend a test to determine the child’s immune status. The following signs indicate a decrease in immunity in a child:

• recurrent respiratory diseases (from 4 times per year);
• allergic reaction to food;
• enlarged lymph nodes;
• increased fatigue;
• sleep disorders;
• growth or physical development retardation

Natural plant immunomodulators

Natural immunomodulators are the best thing that can be given to a child to stimulate the immune system, after mother’s milk, of course. Of the herbal immunomodulators, it is preferable to give children rose hips, aloe, eucalyptus, lemongrass, ginseng, cabbage, beets, radishes and phytoncides (onions, garlic). Many sources also talk about the usefulness of honey and propolis as the best herbal immunomodulators, but giving these products to a child under 3 years of age is highly undesirable, as they immediately cause allergic reactions in children.

It is very important to stimulate the functioning of the immune system through proper nutrition, an active lifestyle, contrast dousing and other physical factors.

They are practically not inferior in effectiveness to synthesized ones, and in the absence of side effects they are superior to them (with the exception of individual intolerance).

List of natural immunomodulators:
• • Ginseng;
• • Walnut;
• • Rose hip;
• • Schisandra chinensis;
• • Thyme;
• • Eleutherococcus;
• • Nettle;
• • Birch;
• • Sea kale;
• • Aralia Manchurian

Based on herbal immodulators, there have been simple recipes for centuries that help maintain human defenses no worse than many modern immunomodulators. See also the answer of the Cytomed specialist to the user’s question What natural immunomodulators are best to give to a child?

to the begining

Immunomodulators are medications that, when used in therapeutic doses, restore the functions of the immune system (effective immune defense).

Classification of immunomodulators

Currently, we distinguish 6 main groups of immunomodulators by origin: microbial, thymic, bone marrow, cytokines, nucleic acids and chemically pure. To a certain extent, this classification is based on the basic principles of the functioning of the immune system. The main activators of innate immunity and inducers of acquired immunity in humans and higher animals are antigens of microbial cells, from which the search, study and creation of immunotropic drugs began. The formation of an immune response occurs under the control of a number of immunoregulatory molecules. Therefore, another direction in the development of immunotropic drugs has become the search, isolation and study of the complex of those substances and molecules that are synthesized in the body during the development of the immune response and regulate it.

Immunomodulators of microbial origin can be divided into three generations. The first drug approved in the early 1950s. In the USA and European countries, for medical use as an immunostimulant, there was a BCG vaccine, which has a pronounced ability to enhance factors of both innate and acquired immunity. First-generation microbial preparations also include drugs such as pyrogenal and prodigiosan, which are polysaccharides of bacterial origin. Currently, due to pyrogenicity and other side effects, they are rarely used.

Second-generation microbial preparations include lysates (Broncho-munal *, IRS-19 *, Imudon *, the new drug Broncho-Vaxom *, which appeared on the Russian pharmaceutical market) and ribosomes (Ribomunil *) of bacteria, which are mainly pathogens of respiratory infections: Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influezae, etc. These drugs have a dual purpose: specific (vaccinating) and nonspecific (immunostimulating).

When studying the cellular components of BCG, it was found that muramyl dipeptide (MDP), the minimal component of peptidoglycan in the bacterial cell wall, had the greatest immunostimulating effect. Due to its high pyrogenicity, MDP has not found clinical use, however, its analogues have been synthesized in Russia and abroad, preserving immunostimulating properties but not having pyrogenic activity. One of them is Likopid, which can be classified as a third generation microbial preparation. It consists of a natural disaccharide - glucosaminylmuramyl and a synthetic dipeptide attached to it - L-alanyl-D-isoglutamine.

Immunomodulators of endogenous origin can be divided into immunoregulatory peptides and cytokines. As is known, the central organs of immunity are the thymus and bone marrow, which regulate the development of cellular and humoral immune responses, respectively. A group of Russian scientists led by Academician R.V. Petrova used these organs to isolate immunoregulatory peptides in order to create drugs that restore cellular and humoral immunity. The impetus for the creation of such drugs was the discovery of a new class of biologically active compounds - thymic peptide hormones, which include the thymosin, thymopoietin families and the serum thymic factor - thymulin.

The ancestor of the first generation thymic drugs in Russia was Taktivin, which is a complex of peptides extracted from the thymus gland of cattle. Preparations containing a complex of thymic peptides also include Timalin, Timoptin, etc., and those containing thymus extracts include Timostimulin * and Vilozen.

The clinical effectiveness of first-generation thymic drugs is beyond doubt, but they have one drawback: they are an unseparated mixture of biologically active peptides that are quite difficult to standardize.

Progress in the field of drugs of thymic origin proceeded through the creation of drugs of the 2nd and 3rd generations - synthetic analogues of natural thymus hormones (alpha1-thymosin and thymopoietin) or fragments of these hormones with biological activity. The latter direction turned out to be the most productive, especially in relation to thymopoietin. Based on one of the fragments, including amino acid residues of the active center of thymopoietin, Thymopentin, registered in the West, and the synthetic hexapeptide Immunofan, an analogue of the 32–36 region of thymopoietin, approved for medical use in Russia, were created.

Another direction in the creation of synthetic thymic drugs was the analysis of the active principles of the complex of peptides and extracts from the thymus. Thus, when studying the composition of the drug Timalin, a dipeptide consisting of tryptophan and glutamine was identified. This dipeptide had pronounced immunotropic activity and became the basis for the creation of the synthetic drug Thymogen, which is L-glutamyl-L-tryptophan.

The ancestor of drugs of bone marrow origin is Myelopid, which includes a complex of bioregulatory peptide mediators - myelopeptides (MP) with a molecular weight of 500–3000 D, produced by pig bone marrow cells. It has now been established that Myelopid includes 6 MPs, each of which has a specific biological effect. It was initially assumed that bone marrow preparations would primarily affect the development of humoral immunity. Subsequently, it was found that various MPs affect different parts of the immune system. Thus, MP-1 increases the functional activity of T-helper cells; MP-2 suppresses the proliferation of malignant cells and significantly reduces the ability of tumor cells to produce toxic substances; MP-3 stimulates the phagocytic activity of leukocytes. The amino acid composition of MP has been completely deciphered, which served as a prerequisite for the development of new synthetic drugs of bone marrow origin. Based on MP-3, Seramil was created, which has an antibacterial effect, and based on MP-2, Bivalen with an antitumor effect was created.

The regulation of the developed immune response is carried out by cytokines - a complex complex of endogenous immunoregulatory molecules, which continue to be the basis for the creation of a large group of both natural and recombinant immunomodulatory drugs. The first group includes Leukinferon and Superlymph, the second group includes Betaleukin, Roncoleukin and Leukomax (molgramostim) *. Leukinferon is a complex of cytokines of the 1st phase of the immune response in their natural ratio, which is obtained in vitro by inducing the leukomass of healthy donors with a vaccine strain of the Newcastle disease virus. The drug contains interleukin-1 (IL-1), IL-6, IL-8, macrophage inhibitory factor (MIF), tumor necrosis factor-alpha (TNF), interferon-alpha complex.

Superlymph is also a complex of natural cytokines produced in vitro during the induction of mononuclear cells in the peripheral blood of pigs with T-mitogen - phytohemagglutinin. The drug contains IL-1, IL-2, IL-6, IL-8, TNF, MIF, transforming growth factor-beta. Superlymph is intended primarily for local use and is practically the first cytokine preparation used for local immunocorrection.

Roncoleukin is a dosage form of recombinant IL-2, which is one of the central regulatory cytokines of the human immune system. The drug is obtained using immune biotechnology methods from producer cells - a recombinant strain of non-pathogenic baker's yeast, the genetic apparatus of which contains the human IL-2 gene.

Betaleukin is a dosage form of recombinant IL-1beta, which plays an important role in the activation of innate immune factors, the development of inflammation and in the first stages of the immune response. The drug is obtained using immune biotechnology methods from producer cells - a recombinant strain of Escherichia coli, in the genetic apparatus of which the human IL-1beta gene is integrated.

The group of chemically pure immunomodulators can be divided into two subgroups: low molecular weight and high molecular weight. The first includes a number of well-known drugs that additionally have immunotropic activity. Their ancestor was levamisole (Dekaris), a phenylimidothiazole, a well-known anthelmintic agent, which was subsequently found to have pronounced immunostimulating properties. Another promising drug from the subgroup of low-molecular immunomodulators is Galavit, a phthalhydrazide derivative. The peculiarity of this drug is the presence of not only immunomodulatory, but also pronounced anti-inflammatory properties. The subgroup of low-molecular immunomodulators also includes three synthetic oligopeptides: Gepon, Glutoxim and Alloferon.

High-molecular, chemically pure immunomodulators obtained using directed chemical synthesis include the drug Polyoxidonium. It is an N-oxidized polyethylene piperazine derivative with a molecular weight of about 100 kD. The drug has a wide range of pharmacological effects on the body: immunomodulatory, detoxifying, antioxidant and membrane protective.

Medicines characterized by pronounced immunomodulatory properties include interferons and interferon inducers. We consider it necessary to separate these drugs into a separate group, since their main pharmacological property is their antiviral effect. However, interferons, as a component of the body's overall cytokine network, are immunoregulatory molecules that affect all cells of the immune system.

Pharmacological action of immunomodulators

Immunomodulators of microbial origin

In the body, the main target for immunomodulators of microbial origin are phagocytic cells. Under the influence of these drugs, the functional properties of phagocytes are enhanced (phagocytosis and intracellular killing of absorbed bacteria are increased), and the production of proinflammatory cytokines necessary for the initiation of humoral and cellular immunity increases. As a result, antibody production may increase and the formation of antigen-specific T-helper and T-killer cells may be activated. The pharmacological effect on immunity of the semisynthetic immunomodulator Lykopid, which is a minimal component of the cell wall of all bacteria, has been most fully studied.

Immunomodulators of thymic origin

Naturally, in accordance with the name, the main target for immunomodulators of thymic origin are T-lymphocytes. With initially low levels, drugs of this series increase the number of T cells and their functional activity. The pharmacological effect of the synthetic thymic dipeptide Thymogen is to increase the level of cyclic nucleotides, similar to the effect of the thymic hormone thymopoietin, which leads to stimulation of differentiation and proliferation of T-cell precursors into mature lymphocytes. At the same time, the immunoregulatory index (CD4/CD8 ratio) is normalized, the ability of T cells to give a proliferative response to T mitogens increases, and the production of corresponding cytokines increases. As a result, the functional activity of innate immune factors – neutrophils, monocytes/macrophages and NK cells – is enhanced. In particular, the ability of monocytes and neutrophils to capture bacteria and produce reactive oxygen species increases.

The pharmacological action of the synthetic immunomodulator of thymic origin Imunofan includes:

• restoration of the production of the thymic hormone thymulin in thymectomized mice to values ​​characteristic of normal animals;
• increased production of IL-2 by lymphocytes stimulated with T-mitogens in in vivo and in vitro experiments;
• immunomodulatory effect on the production of the pro-inflammatory cytokine TNF: increasing its decreased and decreasing its increased formation;
• stimulation in vitro of the formation of IgG, IgA, IgM, and increased synthesis of IgA occurs in the culture of lymphocytes obtained from patients with selective IgA deficiency;
• increased absorption and death of bacteria captured by bacteria;
• in vitro inhibition of IgE formation in cultures of lymphocytes obtained from peripheral blood by patients with allergies;
• adjuvant effect, which manifests itself in increasing the immunogenicity of vaccines against tick-borne encephalitis and hepatitis A.

In addition to immunological effects, Imunofan is able to enhance the body's antioxidant defense by stimulating the synthesis of ceruloplasmin and lactoferrin, as well as catalase activity. Imunofan normalizes lipid peroxidation, suppresses the breakdown of phospholipids in the cell membrane and the formation of arachidonic acid. At the same time, the production of inflammatory mediators decreases.

Immunomodulators of bone marrow origin

The pharmacological action of the immunomodulator of bone marrow origin Myelopid is multifaceted. In the body, the target of this drug is B-lymphocytes. If immuno- or hematopoiesis is impaired, the administration of Myelopid leads to an increase in the general mitotic activity of bone marrow cells and the direction of their differentiation towards mature B-lymphocytes. The expression of pan-B-cell antigens and HLA-DR antigens increases, and the expression of early B-cell markers (Sc-1 antigen) decreases. Due to the presence of the MP-1 component in Myelopid, which acts on T-helper cells, the differentiation of bone marrow cells towards mature T-lymphocytes is also enhanced under its influence.

The MP-3 component, which acts on phagocytosis, is associated with an increase in granulocytopoiesis and functional activity of phagocytic cells caused by the drug. As a result of the implementation of all these properties, the administration of Myelopid ensures an increase in the number of T- and B-cells, as well as phagocytes in the peripheral blood. An increase in their functional activity is manifested in the ability of Myelopid to stimulate the humoral immune response, significantly increasing the level of antibodies. The administration of the drug restores antibody formation in animals exposed to irradiation, cytostatics and antibiotics.

Cytokines

Cytokine preparations of natural origin - Leukinferon and Superlymph - containing a fairly large set of inflammatory cytokines and the first phase of the immune response, are characterized by a multifaceted effect on the human body. These drugs act on cells involved in inflammation, regeneration processes and the immune response.

The pharmacological effect of Superlymph consists of a predominant effect on the effector cells of the innate immune system - neutrophils, monocytes/macrophages and NK cells, which is apparently due to the ability of the drug to increase the level of intracellular calcium - one of the main mediators of cell activation. The drug regulates the migration of phagocytes into the inflammatory focus, enhances the absorption of bacteria by leukocytes and their intracellular death, increases the cytotoxic properties of macrophages, thereby providing the antitumor effect observed in the experiment. By enhancing the production of IL-1 and TNF by monocytes/macrophages, Superlymph activates the mechanisms of both cellular and humoral immunity.

Domestic recombinant cytokine preparations Betaleukin and Roncoleukin, which contain only one cytokine, as well as natural preparations Leukinferon and Superlymph, complex in cytokine composition, have a pleiotropic effect on the human body.

The main pharmacological property of Betaleukin is the enhancement of leukopoiesis and restoration of bone marrow hematopoiesis after the use of cytostatics and X-ray irradiation. This effect of the drug is due to its ability to stimulate the synthesis of colony-stimulating factors - the main inducers of leukopoiesis and stimulants of immunity. Betaleukin has a pronounced immunostimulating effect, since IL-1beta is an activator of all cells of the innate immune system and at the same time an initiator of the development of the first phases of acquired immunity.

The main pharmacological property of Roncoleukin, containing IL-2 - the main growth factor and differentiation of T and NK cells - is the activation and induction of proliferation of target cells - T, B and NK cells containing the CD25 receptor. Roncoleukin acts indirectly on other cells of the immune system through cytokines synthesized by target cells.

Chemically pure immunomodulators

The mechanisms of action of these drugs are best considered using Polyoxidonium as an example. This high-molecular immunomodulator is characterized by a wide range of pharmacological effects on the body, including immunomodulatory, antioxidant, detoxifying and membrane protective effects.

The immunomodulating effect of Polyoxidonium is determined by:

• increasing the ability of neutrophils to capture and kill absorbed Staphylococcus aureus, and the drug enhances the killing of bacteria by neutrophils in the peripheral blood of both healthy donors and patients with chronic granulomatous disease;
• an immunomodulatory effect on the production of proinflammatory cytokines by peripheral blood mononuclear cells of healthy donors, which is manifested by a decrease in elevated and an increase in decreased levels of IL-1, IL-6 and TNF;
• increased cytotoxic activity of NK cells, especially when its initially reduced level;
• activation of resident macrophages of the reticuloendothelial system, which leads to faster elimination of foreign particles from the body;
• increasing the body’s natural resistance to experimental bacterial and viral infections;
• increased antibody formation to T-dependent and T-independent antigens of both animal and microbial origin.
  Polyoxidonium activates immune reactions in animals with severe forms of immunodeficiency, in particular, it enhances antibody formation in:
• mice with congenital thymic aplasia (nude mice);
• mice with artificially created deficiency of the T-immune system (B-mice);
• mice with destruction of the B-immune system artificially induced by the administration of cyclophosphamide;
• old mice characterized by age-related immunodeficiency.

The detoxifying properties of Polyoxidonium are manifested in its ability to reduce the concentration of toxic substances in the blood, for example the level of enterobacteria lipopolysaccharide, in patients with burn disease. In patients with acute pancreatic necrosis, Polyoxidonium significantly reduces the level of malondialdehyde and dienoic acids. The detoxifying properties of the drug are associated with its high molecular weight and the presence of a large number of different active groups on the surface of the molecule. Therefore, it intensively adsorbs soluble toxic substances and microparticles circulating in the blood.

Clinical applications of immunomodulators

The most justified use of immunomodulators seems to be in cases of immunodeficiency, manifested by an increased infectious morbidity. The question arises about the advisability of using immunomodulatory drugs for primary immunodeficiencies, which are based on a genetic defect. Naturally, it is impossible to correct a genetic defect with the help of these drugs. However, anti-infective protection is multicomponent and it can be expected that with some increase in the functional activity of a normally functioning fragment of the immune system using immunomodulators, the “poor performance” of its defective component will be compensated, at least partially.

A significant improvement in the clinical condition and indicators of immune status in patients with reduced levels of all classes of immunoglobulins (general variable immunological deficiency) is observed when they are treated with immunomodulatory drugs that activate phagocytosis, in particular Polyoxidonium. Therefore, well-thought-out use of immunomodulatory therapy in patients with primary immunodeficiencies can provide good clinical results.

The main target of immunomodulatory drugs remains secondary immunodeficiencies, which are manifested by frequent recurrent, difficult-to-treat infectious and inflammatory diseases of all locations and any etiology. Each chronic infectious-inflammatory process is based on changes in the immune system, which are one of the reasons for the persistence of this process. Studying the parameters of the immune system may not always reveal these changes. Therefore, in the presence of a chronic infectious-inflammatory process, immunomodulatory drugs can be prescribed even if an immunodiagnostic study does not reveal significant deviations in the immune status.

As a rule, in such processes, depending on the type of pathogen, the doctor prescribes antibiotics, antifungals, antivirals or other chemotherapeutic drugs. We believe that in all cases where antimicrobial agents are used for symptoms of secondary immunological deficiency, it is advisable to prescribe immunomodulatory drugs.

Below are some general principles for the use of immunomodulators in patients with secondary immunological deficiency.

• Immunomodulators are prescribed in complex therapy simultaneously with antibiotics, antifungals, antiprotozoals or antivirals.
• It is advisable to prescribe immunomodulators as early as possible, from the first day of using a chemotherapeutic etiotropic drug.
• Immunomodulators acting on the phagocytic component of immunity can be prescribed to patients with both identified and undetected disorders of the immune status, i.e., the basis for their use is the clinical picture.
• If a given medical institution has the appropriate material and technical base, it is advisable to use immunomodulators against the background of immunological monitoring, which should be carried out regardless of the presence or absence of initial changes in the immune system.
• When carrying out immunorehabilitation measures, in particular in case of incomplete recovery after an acute infectious disease, immunomodulators can be used as monotherapy.
• A decrease in any parameter of immunity, revealed during an immunodiagnostic study in a practically healthy person, is not necessarily a basis for prescribing immunomodulatory therapy.

Immunomodulators for colds

Colds are one of the most common reasons for using immunostimulants. To make it easier to take and increase the effectiveness of antiviral drugs, they are often combined with immunomodulators. This is completely justified and significantly speeds up the healing process and reduces the number of complications. Thus, the drug Cytovir-3, having antiviral activity and interferonogenic action, taken at the very beginning of the disease, almost halved the acute period of the disease. Its use is also possible for prevention during epidemics.

to the begining

Harm of immunomodulators. Contraindications

Despite all the beneficial properties of this group of drugs, their use should not become uncontrolled - this is fraught with the opposite effect or addiction (typical of some drugs).

Diseases for which the use of any stimulants is contraindicated:
• • Some forms of bronchial asthma;
• • Diabetes;
• • Glomerulonephritis;
• • Toxic goiter;
• • Autoimmune hepatitis;
• • Addison's disease;
• • Multiple sclerosis.

There are a number of other pathologies for which a doctor will never prescribe drugs from this group. Self-administration of medications for the above diseases inevitably causes a relapse of the disease, the consequences of which are unpredictable.

to the begining

What is the difference between immunostimulants and immunomodulators?

Immunostimulants

– forcibly activate the additional reserve of the immune system to fight the virus. The use of the drug allows you to avoid complications of the disease, and treatment is much faster.

Immunomodulators

– change the functioning of the immune system, balance the functioning of the entire system. In some cases, drugs of this group are prescribed to reduce immunity. This is necessary in case of autoimmune diseases.

When are immunostimulants prescribed?

• allergic diseases;
• metabolic disease;
• in the treatment of malignant neoplasms;
• with frequent acute respiratory viral infections or acute respiratory infections;
• for disorders of the endocrine system and metabolism;
• with reduced immunity while taking antibiotics, antidepressants, anticoagulants;
• immunodeficiency of congenital or acquired type;
• fungal and viral infections;
• pathologies of the genitourinary system;
• after internal organ transplant operations.

Contraindications to the use of the drug

• pregnancy and lactation;
• cardiovascular pathologies;
• kidney diseases;
• severe liver damage;
• individual intolerance to the components of the drug;
• bronchial asthma;
• diabetes;
• nervous system disorders;
• childhood.