Biological effects of interleukin-6: Clinical applications in autoimmune diseases and cancers

Biochem Pharmacol. 2015 Sep 1;97(1):16-26. doi: 10.1016/j.bcp.2015.06.009. Epub 2015 Jun 12.

Abstract

Interleukin-6 (IL-6) is a pro-inflammatory cytokine involved in the pathogenesis of various autoimmune and chronic inflammatory diseases. Binding of IL-6 to its receptor (IL-6R) initiates both classical- and trans-signaling pathways. A number of autoimmune diseases are characterized by overproduction of IL-6. Tocilizumab, a humanized monoclonal antibody against IL-6R, blocks IL-6-mediated signaling and has been approved for the treatment of rheumatoid arthritis and Castleman's disease. IL-6 levels are also upregulated in various tumors, and the levels of circulating IL-6 are associated with prognosis in cancer patients. The major issues covered in this commentary include (1) how IL-6-mediated biological effects may lead to the pathogenesis of autoimmune diseases and cancers, (2) the rationale of developing anti-IL-6 strategies for therapeutic purposes, (3) recent advances in anti-IL-6 therapeutics (clinical benefits and adverse events), (4) current knowledge about clinical trials evaluating newly emerging anti-IL-6 treatments, (5) strategies to improve anti-IL-6 therapeutics from both basic and clinical aspects. This commentary provides a useful overview of the role of IL-6 in both autoimmune diseases and cancers from the laboratory as well as clinical perspectives.

Keywords: Autoimmunity; Cancer; Cytokine; IL-6; Signaling pathways; Therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / metabolism
  • Humans
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / metabolism
  • Molecular Targeted Therapy / adverse effects*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / metabolism
  • Signal Transduction / drug effects*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antibodies, Monoclonal, Humanized
  • Antimetabolites, Antineoplastic
  • IL6 protein, human
  • IL6R protein, human
  • Interleukin-6
  • Neoplasm Proteins
  • Receptors, Interleukin-6
  • tocilizumab