title: Biological effects of interleukin-6: Clinical applications in autoimmune diseases and cancers.
abstract: Interleukin-6 (IL-6) is a pro-inflammatory cytokine involved in the pathogenesis of various autoimmune and chronic inflammatory diseases. Binding of IL-6 to its receptor (IL-6R) initiates both classical- and trans-signaling pathways. A number of autoimmune diseases are characterized by overproduction of IL-6. Tocilizumab, a humanized monoclonal antibody against IL-6R, blocks IL-6-mediated signaling and has been approved for the treatment of rheumatoid arthritis and Castleman's disease. IL-6 levels are also upregulated in various tumors, and the levels of circulating IL-6 are associated with prognosis in cancer patients. The major issues covered in this commentary include (1) how IL-6-mediated biological effects may lead to the pathogenesis of autoimmune diseases and cancers, (2) the rationale of developing anti-IL-6 strategies for therapeutic purposes, (3) recent advances in anti-IL-6 therapeutics (clinical benefits and adverse events), (4) current knowledge about clinical trials evaluating newly emerging anti-IL-6 treatments, (5) strategies to improve anti-IL-6 therapeutics from both basic and clinical aspects. This commentary provides a useful overview of the role of IL-6 in both autoimmune diseases and cancers from the laboratory as well as clinical perspectives.
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan, ROC.
authors.forename: Ling-Jun
authors.initials: LJ
authors.lastname: Ho
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan, ROC.
authors.forename: Shue-Fen
authors.initials: SF
authors.lastname: Luo
authors.affiliation: Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan, ROC; Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, ROC. Electronic address: laiandho@gmail.com.
authors.forename: Jenn-Haung
authors.initials: JH
authors.lastname: Lai
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D015850:Interleukin-6; D009363:Neoplasm Proteins; D019947:Receptors, Interleukin-6; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human; C508603:IL6R protein, human; C502936:tocilizumab
keywords: Autoimmunity; Cancer; Cytokine; IL-6; Signaling pathways; Therapy