Interleukin 6: from bench to bedside.
Interleukin (IL)-6 is a pleiotropic cytokine that has important roles in the regulation of the immune response, inflammation, and hematopoiesis. Disruption of IL-6 regulation might, however, affect the immune response and consequently induce immune-mediated inflammatory diseases such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, and Crohn's disease. Overproduction of IL-6 also contributes, through its roles as a growth factor or an antiapoptotic factor, to the development of malignant diseases such as multiple myeloma and renal cancer. Progress in the study of IL-6 has increased our understanding of the pathological roles of this cytokine in these diseases and provided key evidence that antagonizing its activities can be used as a therapeutic strategy. The application of molecular biology techniques to design monoclonal antibodies as therapeutic agents has made it possible to regulate the IL-6 signal to successfully treat diseases that have so far proved refractory to conventional therapies. Blocking IL-6 actions by use of a humanized antibody, tocilizumab, which targets the IL-6 receptor, has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease and Crohn's disease. In this review, we discuss a paradigm of IL-6 from basic science to clinical use.
Nishimoto
Norihiro
N
Laboratory of Immune Regulation in the Graduate School of Frontier Biosciences, Osaka University, Suita City, Japan. norihiro@fbs.osaka-u.ac.jp
Kishimoto
Tadamitsu
T
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000628:therapy; D005871:Castleman Disease / Q000628:therapy; D003424:Crohn Disease / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000628:therapy*; D015850:Interleukin-6 / Q000502:physiology; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors; D016706:Still's Disease, Adult-Onset / Q000628:therapy; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors