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Semin Immunol. 2014 Feb;26(1):88-96. doi: 10.1016/j.smim.2014.01.009. Epub 2014 Mar 1.

A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy.

Author information

  • 1Department 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.
  • 2Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
  • 3Department 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.
  • 4Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka 565-0871, Japan. Electronic address: kishimoto@ifrec.osaka-u.ac.jp.

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.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Autoimmunity; IL-6; Inflammation; Tocilizumab

PMID:
24594001
[PubMed - indexed for MEDLINE]
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