Tumor necrosis factor and interferon gamma: relevance for immune regulation and genetic predisposition to autoimmune disease.
The role of TNF-alpha and IFN-gamma in various models of autoimmune disease were analyzed. These include murine models of lupus, type 1 diabetes in NOD mice and the adjuvant arthritis model in rats. Rather than being involved mainly in the effector arm of the inflammatory process of autoimmune organ destruction, our data suggest a primary involvement of these cytokines in some of the basic mechanisms of the autoimmune process. Evidence has been presented that emphasizes the possibility of the involvement of TNF-alpha in the genetic predisposition to SLE. Based on the data presented, one should be cautious in extrapolating the effects of these cytokines in various in vitro systems to the in vivo situation.
Jacob
C O
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Department of Inflammation Biology and Immunology, Syntex Research, Palo Alto, CA 94303.
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology; D008817:Mice, Mutant Strains / Q000235:genetics / Q000276:immunology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma