title: Therapeutic targeting of the interleukin-6 receptor.
abstract: Interleukin (IL)-6 is a typical cytokine featuring redundancy and pleiotropic activity. It contributes to host defense against pathogens, but dysregulation of IL-6 production plays a significant pathological role in various autoimmune and inflammatory diseases. Because IL-6 blockade was expected to constitute a novel strategy for the treatment of such diseases, tocilizumab, a humanized anti-IL-6 receptor antibody (anti-IL-6RAb), was developed. Clinical trials have demonstrated the efficacy of anti-IL-6RAb for patients with rheumatoid arthritis, Castleman's disease, and juvenile idiopathic arthritis, resulting in approval of this innovative biologic for the treatment of these diseases, and it can be expected to become a novel drug for various other autoimmune and inflammatory diseases. In murine models of autoimmune diseases, anti-IL-6RAb induces Treg and inhibits Th17 and/or Th1 differentiation, indicating that anti-IL-6RAb may be able to repair Th17/Treg imbalance in human diseases as well.
authors.affiliation: Laboratory of Immunoregulation, Graduate School of Frontier Biosciences, and Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Graduate School of Medicine, Osaka University, Osaka, 565-0871 Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
authors.forename: Masashi
authors.initials: M
authors.lastname: Narazaki
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016032:Randomized Controlled Trials as Topic; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects; D058504:Th17 Cells / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab