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Logo of mjafiGuide for AuthorsAbout this journalExplore this journalMedical Journal, Armed Forces India
 
Med J Armed Forces India. 1995 July; 51(3): 149–150.
Published online 2017 June 26. doi:  10.1016/S0377-1237(17)30954-1
PMCID: PMC5530040

IMMUNOMODULATION — CLINICAL APPLICATIONS

SK DHAM, VSM*

Advances in basic and clinical immunology have uncovered mechanisms of aberrant immune regulation underlying many immune mediated disorders. The disordered immune regulation is typically characterized by depressed cellular immune responses and exaggerated humoral immunity. Correction of immune defects by suppression of hyperactive responses or enhancement of depressed immuno-regulatory responses constitutes immunomodulation and has proved to be beneficial in a number of autoimmune disorders. Most immunomodulators in current clinical use produce non-specific alterations in the host response. Recent emphasis has however shifted to the development of selective immunomodulators which are directed only against the abnormal immune response.

Immunosuppressive drugs are used to modify the auto-immune processes in certain situations of immune stimulation. A number of drugs have been extensively used and have stood the test of time. These include corticosteroids, cytotoxic drugs like cyclophosphamide, chlorambucil and methotrexate, cyclosporin A, intravenous immunoglobulins, and anti-lymphocyte globulins. These have proved to be beneficial in a number of hematological, renal, neurological and connective tissue disorders. Physical methods tried are plasmapheresis for Gullian-Barre' syndrome, myasthenia gravis, multiple sclerosis, and lupus nephritis. Thymectomy has been shown to be beneficial in myasthenia gravis. Severe toxicity limits the use of ionizing radiation. Today it is used only as a pre-transplantation procedure. With the development of hybridoma technology a variety of monoclonal antibodies have been developed and tried against the mediators of inflammation including tumor necrosis factor α [1], interleukin 6 [2], and the adhesion molecule CD 11b/18. Usefulness of these, however, is limited by the development of autoimmune antibodies. Efforts are on to produce less immunogenic hybrid monoclonal antibodies by splicing the murine variable region of immunoglobulin gene with the human constant region gene. Interleukin-1 receptor antagonist is undergoing clinical trials in the treatment of rheumatoid arthritis, septic shock [3] and inflammatory bowel disease. T-cell vaccination by injecting low doses of cross linked autoreactive T-cells and inhibition of class II HLA antigen presentation using peptides and antibodies have proved promising in animal trials. FK-506 and rapamycin are available and have the promise to replace cyclosporin A. Immune tolerance can also be induced by the administration of oral antigens [4].

Levamisole, an anti-helminthic drug, potentiates the nonspecific immune response. Its use has been limited due to its unpredictable effect and the occurrence of agranulocytosis. A number of thymic peptide extracts including thymosin, thymomodulin and thymopentin have immunostimulatory actions and have potential application in the treatment of viral and fungal infections, primary immunodeficiency states, small cell carcinoma of the lung, and rheumatoid arthritis. Adoptive immunity using interleukin-2 and lymphokine activated killer cells has been found useful in the treatment of malignant melanoma and renal cell carcinoma. OK-432, an extract from a strain of Streptococcus pyogenes, augments natural killer cell activity and is beneficial in the treatment of head-and-neck, gastrointestinal, and lung malignancies. Certain bacterial antigens like mycobacterial heat-shock proteins have superantigen activity and are capable of stimulating a large number of T-lymphocytes. BCG vaccine has been used with benefit in the treatment of bladder carcinoma, malignant melanoma and leprosy. Interferons have been the most widely used immunostimulatory agents [5] and have been found effective in the treatment of infections especially hepatitis B and C [6], Kaposi's sarcoma and a number of hematological malignancies like chronic myeloid leukemia [7], multiple myeloma, and lymphomas. Interferons have significant effects on cell differentiation, cell growth and on the expression of cell surface antigens. They enhance T-cell mediated cytotoxicity and natural killer cell activity.

With a better understanding of immunology, the importance of immune responses has been increasingly recognized not only in autoimmune disorders but also in a number of other disease states like infections and malignancies. Immunoregulatory agents are being increasingly used not only to modify the aberrant immune reactivity but also to induce a desirable immune response. Till the recent past these agents were non-specific and their use was associated with a number of side effects. Specific agents have now been developed and many more are likely to be available for clinical use in the near future. Since these agents will be used in a number of common disorders in every branch of medicine, it is a essential that every clinician be familiar with these agents. Induction of antigen specific immunological tolerance remains an unfulfilled goal.

REFERENCES

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