Interleukin-12.
Interleukin-12 (IL-12) is a newly characterized cytokine that has a unique heterodimeric structure. It was initially cloned from B lymphoblastoid cell lines, but the majority of IL-12 is produced by macrophages/monocytes following appropriate stimulation. IL-12 can (1) enhance the cytolytic activity of a number of effector cells including T cells, natural killer (NK) cells, lymphokine activated killer (LAK) cells, and macrophages, (2) increase proliferation of activated NK and T cells, (3) induce production of cytokines, such as interferon gamma, (4) stimulate the induction of TH1 cells, (5) upregulate a number of cell surface molecules, (6) inhibit IgE secretion, and (7) act as a synergistic factor for hematopoietic stem cells. Based on these potent immunomodulatory activities, IL-12 has been evaluated in several disease models for parasitic infections and malignancies. Marked activity of IL-12 against both Leishmania and Toxoplasma has been reported. Likewise, antimetastatic and antitumor activity, including tumor regression, has been observed against a number of murine malignancies treated with IL-12 using doses that result in little toxicity. The results suggest that IL-12 may be a useful cytokine for the treatment of a number of diseases.
Brunda
M J
MJ
Department of Oncology, Hoffman-LaRoche, Inc., Nutley, NJ 07110.
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D018664:Interleukin-12; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D007896:Leishmaniasis / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects; D008216:Lymphocytic Choriomeningitis / Q000628:therapy; D051379:Mice; D009374:Neoplasms, Experimental / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000628:therapy
D016207:Cytokines; D007378:Interleukins; D018664:Interleukin-12