The IL-6/gp130/STAT3 signaling axis: recent advances towards specific inhibition

Curr Opin Immunol. 2015 Jun;34:75-82. doi: 10.1016/j.coi.2015.02.008. Epub 2015 Mar 6.

Abstract

Interleukin-6 has long been recognized as a prototypic pro-inflammatory cytokine that is involved in the pathogenesis of all inflammatory diseases. Activation of the gp130 homodimer by IL-6 leads to the initiation of Jak/STAT signaling, a pathway that is often constitutively switched on in inflammatory malignancies. However, a plethora of studies in the last decade has convincingly shown that only signaling via the soluble IL-6R (trans-signaling) accounts for the deleterious effects of IL-6, whereas classic signaling via the membrane-bound receptor is essential for the regenerative and anti-bacterial effects of IL-6 (classic signaling). In this review, we highlight recent developments in the field of IL-6 research, and specifically focus on advances towards a safe and specific inhibition of IL-6 trans-signaling.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism*
  • Receptors, Interleukin-6 / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction*

Substances

  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • tocilizumab