Interleukin-6 signalling in health and disease

F1000Res. 2020 Aug 20:9:F1000 Faculty Rev-1013. doi: 10.12688/f1000research.26058.1. eCollection 2020.

Abstract

Biochemically, interleukin-6 belongs to the class of four-helical cytokines. The cytokine can be synthesised and secreted by many cells. It acts via a cell surface-expressed interleukin-6 receptor, which is not signalling competent. This receptor, when complexed with interleukin-6, associates with the signalling receptor glycoprotein 130 kDa (gp130), which becomes dimerised and initiates intracellular signalling via the Janus kinase/signal transducer and activator of transcription and rat sarcoma proto oncogene/mitogen-activated protein kinase/phosphoinositide-3 kinase pathways. Physiologically, interleukin-6 is involved in the regulation of haematopoiesis and the coordination of the innate and acquired immune systems. Additionally, interleukin-6 plays an important role in the regulation of metabolism, in neural development and survival, and in the development and maintenance of various cancers. Although interleukin-6 is mostly regarded as a pro-inflammatory cytokine, there are numerous examples of protective and regenerative functions of this cytokine. This review will explain the molecular mechanisms of the, in part opposing, activities of the cytokine interleukin-6.

Keywords: ADAM17; IL-6; IL-6R; gp130; sIL-6R; sgp130Fc; trans-signalling.

Publication types

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

MeSH terms

  • Cytokine Receptor gp130 / physiology*
  • Humans
  • Interleukin-6 / physiology*
  • Neoplasms
  • Proto-Oncogene Mas
  • Receptors, Interleukin-6 / physiology*
  • Signal Transduction*

Substances

  • Interleukin-6
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Receptors, Interleukin-6
  • Cytokine Receptor gp130

Grants and funding

The work of Stefan Rose-John has been supported by grants of the Deutsche Forschungsgemeinschaft Bonn, Germany, under the grant numbers CRC841, project C1, and CRC877, project A1, and by the German Excellence Cluster "Inflammation at Interfaces".