Classification by source of origin
Immunomodulating agents are globally divided into two major groups based on their origin:
- Exogenous immunomodulators. These are substances that are initially foreign to our body. Their nature is extremely diverse. This group includes natural and synthesized chemical compounds, as well as various microbial components (adjuvants, chemical compounds). Furthermore, physical factors such as radiation or climatic conditions are also considered exogenous factors capable of modulating immunity.
- Endogenous immunomodulators. These compounds are normally synthesized by the body itself, particularly by immunocompetent cells. Chemically, they are predominantly oligopeptides. Their main task is to activate immunity by enhancing the proliferation and functional activity of immune cells. This extensive group includes interferons ($\alpha$, $\beta$, $\gamma$), various interleukins, thymus peptides, tumor necrosis factors (TNFs), chemokines, myelopeptides, colony-stimulating factors (CSFs), and transforming growth factor (TGF).
Division by target action
Regardless of their origin, any of these substances can exert a dual effect on the immune system. Based on the direction of the effect, a distinction is made between immunostimulants (activate defense mechanisms) and immunosuppressants (suppress immune responses).
- Immunostimulants. These include adjuvants: polymers, sorbents, polysaccharides, lipopolysaccharides. This group also includes BCG complexes (known as Freund's adjuvant), bacterial components (muramyl dipeptide, prodigiosin, and salmazan). Stimulants also include chemical compounds (e.g., levamisole) and endogenous molecules (cytokines, thymus, and bone marrow peptides).
- Immunosuppressants. This group includes cytostatics (amino acid, enzyme, and purine antagonists, such as 6-mercaptopurine), hormonal agents (glucocorticosteroids), and biological drugs. The latter include monoclonal antibodies targeting immunocompetent cell receptors and antilymphocyte serum. Physical factors—such as X-ray or $\gamma$-radiation—also possess a powerful suppressive effect.
Main pharmacological groups
Modern medicine uses numerous drugs created on the basis of immunomodulating substances:
- Genetically engineered cytokine drugs. These include interferon inducers, interferons themselves, and interleukins (IL-1$\beta$ or beta-leukin, IL-2, IL-3, IL-6).
- Thymus gland drugs. Obtained either through genetic engineering synthesis or as extracts from bovine thymus. Well-known representatives include taktivin, thymosin, tutilin, and thymopoietin.
- Bone marrow drugs. Include myelopeptides extracted from natural raw materials and their recombinant analogues.
- Drugs of microbial origin. This is an extensive group of exogenous modulators. Many of them are created based on lipopolysaccharides of gram-negative bacteria: pyrogenal is synthesized from Pseudomonas aeruginosa, prodigiosin from B. prodigiosum, and salmazan from salmonellae. Modified components of the bacterial cell wall are also used (licopid, which is a modified muramyl dipeptide), ribosomal drugs (ribomunyl), VP-4 vaccine, and sodium nucleinate (salt of yeast low-molecular-weight RNA). Lysates and components of Klebsiella, streptococci, and pneumococci containing membrane proteoglycans are widely used.
Areas of clinical application
Immunomodulating agents have found the widest application in the treatment and prevention of a range of pathological conditions. First and foremost, they are prescribed for primary and secondary immunodeficiencies to restore the body's defense functions.
They are critically important in oncological practice and transplantology, where immunosuppressants are used to prevent the rejection of transplanted organs and tissues. In addition, immunomodulators are actively used in the treatment of immunopathological and allergic diseases. Microbial and other drugs have proven effective in the treatment of infectious diseases, acting as agents for immunocorrection and immunoprophylaxis, as well as in the therapy of non-infectious diseases involving the immune system in their pathogenesis.
Briefly: answers to topical questions
What is the mechanism of action of levamisole on the immune system?
The mechanism of action of levamisole lies in its predominant effect on the T-cell link of immunity. The drug exerts the following effects:
- Regulation of differentiation — influences the maturation of T-lymphocytes.
- Enhancement of reactivity — increases the response of T-cells to antigens and mitogens, as well as their proliferative potential.
- Stimulation of secretion — increases the production of lymphokines (cytokines).
- Increase in cytotoxicity — enhances the effector functions of T-cells.
- Enhancement of cooperation — improves the interaction of T- and B-lymphocytes, stimulating the synthesis of immunoglobulins.
Which cytostatics are used as immunosuppressants?
Cytostatics of the following groups are used as immunosuppressants:
- Antimetabolites — azathioprine, mycophenolate mofetil.
- Alkylating agents — cyclophosphamide.
- Purine antagonists — 6-mercaptopurine.
- Amino acid and enzyme antagonists.
These drugs are used to suppress unwanted immune reactions, including rejection, allergic, and autoimmune processes.
What are the components of Freund's complete adjuvant?
Freund's complete adjuvant contains components of an oil emulsion and bacterial antigens. The preparation contains the following substances:
- Lipids and emulsifiers — lanolin, liquid paraffin, and an emulsifier.
- Bacterial component (Mycobacterium bovis) — BCG extracts (vaccine strain).
The addition of mycobacteria ensures effective induction of the primary immune response due to the preliminary stimulation of innate immunity cells.
What interferon inducer drugs exist?
Interferon inducers include:
- Tilorone.
- Meglumine acridoneacetate.
- Sodium oxodihydroacridinylacetate.
- Polyadenylic acid + polyuridylic acid.
- Imidazolylethanamide pentandioic acid.
- Oxyethylammonium methylphenoxyacetate.
- Azoximer bromide.
To memorize thymus drugs, pay attention to the root "thymo-" or the letter "T" at the beginning of the name: Taktivin, Thymosin, Tutilin, Thymopoietin.
Class and exam questions
What is the difference between endogenous and exogenous immunomodulators?
Endogenous ones are synthesized by the body itself (predominantly oligopeptides, e.g., cytokines), while exogenous ones are introduced from the outside and are foreign substances of chemical or microbial nature.
Which drugs belong to immunosuppressants?
These include cytostatics (e.g., 6-mercaptopurine), glucocorticosteroids, antilymphocyte serum, monoclonal antibodies to immune cell receptors, and physical radiation exposure.
What are immunomodulators of microbial origin derived from?
They are created based on lipopolysaccharides of gram-negative bacteria (e.g., Pseudomonas aeruginosa), modified cell wall components, lysates of streptococci and pneumococci, as well as yeast RNA.
What else to study on this topic
- Mechanisms of action of adjuvants (BCG complexes, sorbents, polymers)
- Genetically engineered cytokine drugs (interleukins and interferons)
- Features of the use of immunosuppressants in transplantology
- Ribosomal drugs and bacterial lysates
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