title: A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy.
abstract: Interleukin-6 (IL-6) is a cytokine with redundant and pleiotropic activities, and its synthesis is tightly regulated by transcriptional and posttranscriptional mechanisms. When infections and tissue injuries occur, IL-6 synthesis is promptly induced and provides an emergent signal that contributes to host defense through the stimulation of acute-phase responses, immune reactions, and hematopoiesis. After the environmental stress is removed from the host, the production of IL-6 is terminated. However, dysregulated continual synthesis of IL-6 is involved in the development of chronic inflammatory autoimmune diseases. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Worldwide clinical trials have demonstrated the outstanding efficacy of tocilizumab in rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease; thus, a new era has come for the treatment of these diseases, which were previously considered intractable. Moreover, favorable results from off-label use of tocilizumab strongly suggest that it will be widely applicable for various refractory inflammatory autoimmune diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated in order to investigate the pathogenesis of specific diseases and to facilitate the development of more specific therapeutic strategies.
authors.affiliation: Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; Department of Immunopathology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Narazaki
authors.affiliation: Department of Immunopathology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan; Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogata
authors.affiliation: Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. Electronic address: kishimoto@ifrec.osaka-u.ac.jp.
authors.forename: Tadamitsu
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D012323:RNA Processing, Post-Transcriptional; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014158:Transcription, Genetic
chemical_list: D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C502936:tocilizumab
keywords: Autoimmunity; IL-6; Inflammation; Tocilizumab