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: Toshio Tanaka, Masashi Narazaki, Atsushi Ogata, Tadamitsu Kishimoto
• Journal: Seminars in immunology (Semin Immunol) Vol. 26 Issue 1 Pg. 88-96 (Feb 2014) ISSN: 1096-3618 [Electronic] England
• PMID: 24594001 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Acute-Phase Proteins
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Interleukin-6
• Receptors, Interleukin-6
• tocilizumab

Topics

• Acute-Phase Proteins (biosynthesis)
• Animals
• Antibodies, Monoclonal (pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized (pharmacology, therapeutic use)
• Autoimmune Diseases (drug therapy, genetics, immunology, metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Immunomodulation (drug effects)
• Inflammation (drug therapy, genetics, immunology, metabolism)
• Interleukin-6 (genetics, metabolism)
• RNA Processing, Post-Transcriptional
• Receptors, Interleukin-6 (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Transcription, Genetic