Immunostimulant

Immunostimulator

1. IMMUNOSTIMULANT SHAHJAHAN Neelkanth College of Pharmacy Education Jaunpur

2. Introduction Immunostimulants , also known as  immunostimulators , are substances (drugs and nutrients) that stimulate the  immune system  by inducing activation or increasing activity of any of its components. Two main compounds are able to enhance immune responses including adjuvants and immunostimulants . An adjuvant is a substance combined with an antigen for increasing its immune response, but an immunostimulant can induce the immune response without injection with an antigen.

3. Concept of Immunostimulant Immunostimulants are substances that activate the immune system of humans and animals for prevention of diseases and improvement of the body’s natural resistance to various viral and bacterial infections. In general, Immunostimulants induce synthesis of specific antibodies and cytokines for treatment of infectious diseases. Examples of immunostimulant- Bacillus Calmette Guerin, Bacterial products act by Enhancement of B and T cell-mediated responses leading to phagocytosis, and resistance to infection Levamisole act by Induction of B and T lymphocytes, monocytes , and macrophages Thalidomide Drugs - Therapeutic effects in rheumatoid arthritis and angiogenesis Recombinant cytokines - Generation of interferon and interleukins to stimulate effective immune responses

4. Classification There are two main categories of immunostimulants : Specific immunostimulants  provide antigenic specificity in immune response, such as vaccines or any  antigen Non-specific immunostimulants  act irrespective of antigenic specificity to augment immune response of other antigen or stimulate components of the immune system without antigenic specificity, such as  adjuvants  and non-specific immunostimulators .

5. Immunostimulatory Drug Levamisole ( Ergamisol ) Levamisole is a synthetic drug inducing B and T lymphocytes, monocytes , and macrophages. It was used in adjuvant therapy with 5- fluorouracil after surgical resection in patients with Duke’s stage C colon cancer Levamisole has been successfully used in combination with polymers for treatment of dermatologic disorders. For example, it was combined with cimetidine for treating recalcitrant warts, and with prednisolone for treating aphthous ulcers of the mouth . Side effects are allergy, nausea, flu, and muscle pain.

6. Isoprinosine ( Inosiplex / Imunovir ) Isoprinosine is a combination of inosine , acetamidobenzoic acid, and dimethylaminoisopropanol . Isoprinosine stimulates biochemical processes in macrophages, increases the production of interleukin, increased synthesis of antibodies, enhances the proliferation of T-lymphocytes , natural killer cells. It stimulates the chemotactic and phagocytic activity of monocytes , macrophages and polymorphonuclear cells . Isoprinosine inhibits the replication of DNA and RNA viruses by binding with ribosome cells and changes its stereochemical structure .

7. Indication- Immunodeficiency, accompanied by the development of diseases, caused by the Herpes simplex virus, Varicella zoster, measles virus, Epstein-Barr virus, the development of subacute sclerosing panencephalitis acute viral encephalitis Side effect Metabolism: transient increase in uric acid in the serum and urine digestive system: nausea, vomiting, epigastric pain, constipation, diarrhea, a temporary increase in liver transaminases . Dermatological reactions:  xerosis . Allergic reactions: skin rash, itch. CNS: headache, dizziness, nervousness, sleep disorders (drowsiness, insomnia), slackness, a feeling of fatigue. Other:  polyuria , joint pain, worsening of gout, weakness.

8. Bacterial products BCG (Bacillus Calmette–Guérin ) BCG vaccine   is  primarily used against tuberculosis (TB). The vaccine was developed over a period of 13 years, from 1908 to 1921, by French bacteriologists Albert Calmette and Camille Guérin who named the product Bacillus Calmette- Guérin , or BCG. The immunostimulatory effects of bacteria and bacterial products are due to the release of cytokines. Live Bacillus Calmette-Guerin (BCG) is an attenuated, live culture of the bacillus of Calmette and Guerin strain of Mycobacterium bovis .

9. BCG enhances both B and T cell-mediated responses leading to phagocytosis and resistance to infection. BCG is given as a single  intradermal  injection at the insertion of the deltoid. If BCG is accidentally given subcutaneously, then a local abscess may form (a "BCG- oma ") that can sometimes ulcerate, and may require treatment with antibiotics immediately. Its side effects are hypersensitivity, fever, shock, and immune complex disease. Use of the BCG vaccine may provide protection against COVID‑19. However, epidemiologic observations in this respect are ambiguous. The WHO does not recommend its use for prevention as of 12 January 2021. As of January 2021, twenty BCG trials are in various clinical stages.

10. Recombinant Cytokines Cytokines are a group of proteins involved in the innate and adaptive immune systems. Recombinant cytokines are generally designed to enhance immunity either by achieving generalized immunostimulation or stimulating specific immune cells. Several interferons and interleukins are suggested to stimulate effective immune responses. Interferons could be obtained from trout leucocytes after stimulation with mitogens . It was able to cause an in vitro resistance against pancreatic necrosis virus in trout cells. In mammalian, low doses of interferon could induce stable positive results without side effects

11. On the other hand, vaccination of animals with the recombinant IL2 against different infections increased the protective effects. However, IL-2 was a very toxic compound in high doses causing side effects such as fever and diarrhea.

12. Complex carbohydrates Several types of the complex carbohydrates were described as follows Glucans Glucans is an important class of immunostimulants is the β-(1→3)-linked chain of glucose units. The main chain has β-(1→6)-branched glucose units. The β- glucans were obtained from highly conserved structural components of cell walls in fungi, algae, yeast. Glucan might also be helpful to prevent the carcinogenic effects of aflatoxin . β- glucan was considered as a stimulator of cellular immunity.

13. Plant-derived immunostimulants Natural plant product promote various activities such as anti-stress, growth promotion, appetite stimulation, immunostimulation , aphrodisiac and antimicrobial properties, due to the active substances such as alkaloids, flavanoids pigments, phenolics , terpenoids , steroids, and essential oils . Ocimum sanctum ( Tulsi ): Leaves of O. sanctum containing water-soluble phenolic compounds and various other constituents may act as an immunostimulant. Phyllanthus emblica (Amla): P. emblica has antioxidant, anti-fungal, anti-microbial, and anti inflammatory activities. Amla fruit pulp contains a large amount of vitamin C as an immunostimulant . Azadirachta indica ( Neem ): A. indica possesses antihuman immunodeficiency virus, anti-tumor, and antimicrobial activities. Azadirachtin , a triterpenoid derived from A. indica , enhanced respiratory burst activities, the leukocyte count and the primary and secondary antibody responses