Interleukin-6: Biology, signaling and strategies of blockade

Cytokine Growth Factor Rev. 2015 Oct;26(5):475-87. doi: 10.1016/j.cytogfr.2015.07.004. Epub 2015 Jul 4.

Abstract

Interleukin-6 (IL-6) is one of the most important inflammatory cytokines. IL-6 is unique in signaling via a membrane bound and a soluble receptor. Intriguingly, these two pathways strongly differ in their biologic consequences. While classic IL-6 signaling via the membrane bound receptor is mainly regenerative and protective, IL-6 trans-signaling via the soluble IL-6R is rather pro-inflammatory. Intracellular signaling of IL-6 in response to receptor activation is through STAT-dependent and STAT-independent signaling modules, which are regulated by a complex regulatory network. The complex biology of IL-6 has consequences for therapeutic targeting of this cytokine. We hypothesize that specific inhibition of the trans-signaling pathway may be superior to global blockade of IL-6 activity with help of antibodies directed against IL-6 or IL-6R.

Keywords: Cytokine; Inflammation; Receptor; Signal transduction; Trans-signaling.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Inflammation / immunology
  • Inflammation / pathology
  • Interleukin-6 / immunology*
  • Receptors, Interleukin-6 / immunology*
  • STAT Transcription Factors / immunology*
  • Signal Transduction / immunology*

Substances

  • IL6 protein, human
  • IL6R protein, human
  • Interleukin-6
  • Receptors, Interleukin-6
  • STAT Transcription Factors