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Interleukin-12 (IL-12) is a pleiotropic cytokine, formerly termed cytotoxic lymphocyte maturation factor (CLMF) or natural killer cell stimulatory factor (NKSF), which is produced primarily by stimulated macrophages. IL-12 exerts a variety of biological effects on human T and natural killer cells. Apart from promotion of Th1 development and its ability to promote cytolytic activity it mediates some of its physiological activities by acting as a potent inducer of interferon (IFN) gamma production and the stimulation of other cytokines from peripheral blood T and NK cells,. IFN-g then enhances the ability of the phagocytic cells to produce IL-12 and other proinflammatory cytokines. Thus, IL-12 induced IFN-g acts in a positive feedback loop that represents an important amplifying mechanism in the inflammatory response to infections. Its role in directing development of a Th1 type immune response from naive T cells demonstrates its critical role in regulation of the immune response and strongly suggests its potential usefulness in cancer therapy. IL-12 is a disulfide-linked heterodimeric cytokine composed of a 35 kDa light chain (p35) and a 40 kDa heavy chain (p40) resulting in the only biologically active 70 kDa (p70) form of IL-12. The p40 subunit can also form a homodimer which has been shown to be able to bind the IL- 12 receptor and thus acts as an IL-12 antagonist. Additionally, the p40 subunit has been found to be expressed in a high excess over p70. The critical role of IL-12 in several pathogeneses has been shown. Increased plasma levels were found neurological disorders. Significant elevations were measured in autistic patients, and in multiple sclerosis patients. High levels of IL-12 have also been reported for autoimmune diseases and chronic inflammatory reactions, such as in synovial fluid of patients with osteoarthritis, rheumatoid arthritis and seronegative spondylarthropathies, in Sjogren's syndrome patients and atherosclerosis. Changes in the expressing levels of IL-12 are reported for a large number of both bacterial and viral infections such as obstructive jaundice, septic shock, infection with Mycobacterium tuberculosis, HIV infection. Interleukin-12 also plays a crucial role in allograft rejection and selected inflammatory skin lesions. Synonyms: Cytotoxic lymphocyte maturation factor, CLMF, NK cell stimulatory factor, NKSF1 Synonyms: Cytokine synthesis inhibitory factor, CSIF

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