Therapeutic targeting of the interleukin-6 receptor

Annu Rev Pharmacol Toxicol. 2012;52:199-219. doi: 10.1146/annurev-pharmtox-010611-134715. Epub 2011 Sep 9.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology
  • Cell Differentiation / drug effects
  • Disease Models, Animal
  • Drug Delivery Systems / methods
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Interleukin-6 / immunology
  • Randomized Controlled Trials as Topic
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / immunology*
  • T-Lymphocytes, Regulatory / drug effects
  • Th1 Cells / drug effects
  • Th17 Cells / drug effects

Substances

  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • Receptors, Interleukin-6
  • tocilizumab