The paradigm of IL-6: from basic science to medicine.
IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Its activities are shared by IL-6-related cytokines such as leukemia inhibitory factor and oncostatin M. The pleiotropy and redundancy of IL-6 functions have been identified by using a unique receptor system comprising two functional proteins: an IL-6 receptor (IL-6R) and gp130, the common signal transducer of cytokines related to IL-6. Signal transduction through gp130 is mediated by two pathways: the JAK-STAT (Janus family tyrosine kinase-signal transducer and activator of transcription) pathway and the Ras mitogen-activated protein kinase pathway. The negative regulators of IL-6 signaling have also been identified, although the physiological roles of the molecules are not yet fully understood. The pathological roles of IL-6 have also been clarified in various disease conditions, such as inflammatory, autoimmune, and malignant diseases. On the basis of the findings, a new therapeutic approach to block the IL-6 signal using humanized anti-IL-6R antibody for rheumatoid arthritis, Castleman's disease, and multiple myeloma has been attempted.
Naka
Tetsuji
T
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Japan. naka@imed3.med.osaka-u.ac.jp
Nishimoto
Norihiro
N
Kishimoto
Tadamitsu
T
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*
D015850:Interleukin-6; D019947:Receptors, Interleukin-6