Interleukin-6 blockade in ocular inflammatory diseases

Clin Exp Immunol. 2014 Jun;176(3):301-9. doi: 10.1111/cei.12295.

Abstract

Interleukin-6 (IL-6) is a key cytokine featuring redundancy and pleiotropic activity. It plays a central role in host defence against environmental stress such as infection and injury. Dysregulated, persistent interleukin (IL)-6 production has been implicated in the development of various autoimmune, chronic inflammatory diseases and even cancers. Significant elevation of IL-6 has been found in ocular fluids derived from refractory/chronic uveitis patients. In experimental autoimmune uveitis models with IL-6 knock-out mice, IL-6 has shown to be essential for inducing inflammation. IL-6 blockade can suppress acute T helper type 17 (Th17) responses via its differentiation and, importantly, can ameliorate chronic inflammation. Tocilizumab, a recombinant humanized anti-IL-6 receptor antibody, has been shown to be effective in several autoimmune diseases, including uveitis. Herein, we discuss the basic biology of IL-6 and its role in development of autoimmune conditions, focusing particularly on non-infectious uveitis. It also provides an overview of efficacy and safety of tocilizumab therapy for ocular inflammatory diseases.

Keywords: autoimmune diseases; interleukin-6; monoclonal antibodies; tocilizumab; uveitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Eye Diseases / drug therapy
  • Eye Diseases / genetics
  • Eye Diseases / immunology
  • Eye Diseases / metabolism*
  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Molecular Targeted Therapy
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Receptors, Interleukin-6 / metabolism*
  • Signal Transduction

Substances

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