IL-6 in autoimmune disease and chronic inflammatory proliferative disease.
Interleukin 6 (IL-6), which was originally identified as a B-cell differentiation factor, is now known to be a multifunctional cytokine that regulates the immune response, hematopoiesis, the acute phase response, and inflammation. Deregulation of IL-6 production is implicated in the pathology of several disease processes. The expression of constitutively high levels of IL-6 in transgenic mice results in fatal plasmacytosis, which has been implicated in human multiple myeloma. Increased IL-6 levels are also observed in several diseases, including rheumatoid arthritis (RA), systemic-onset juvenile chronic arthritis (JCA), osteoporosis, and psoriasis. IL-6 is critically involved in experimentally induced autoimmune disease, such as antigen-induced arthritis (AIA), and experimental allergic encephalomyelitis. All these clinical data and animal models suggest that IL-6 plays critical roles in the pathogenesis of autoimmune diseases. Here we review the evidence for the involvement of IL-6 in the pathophysiology of autoimmune diseases and chronic inflammatory proliferative diseases (CIPD) and discuss the possible molecular mechanisms of its involvement.
Ishihara
Katsuhiko
K
Department of Molecular Oncology (C7), Graduate School of Medicine, Osaka University, 2-2 Yamada-oka Suita, Osaka 565-0871, Japan.
Hirano
Toshio
T
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000503:physiopathology; D005544:Forecasting; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010954:Plasmacytoma / Q000235:genetics; D011110:Polymorphism, Genetic; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology
D001323:Autoantibodies; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators