IL-6 biology: implications for clinical targeting in rheumatic disease

Nat Rev Rheumatol. 2014 Dec;10(12):720-7. doi: 10.1038/nrrheum.2014.127. Epub 2014 Aug 19.


IL-6 has been linked to numerous diseases associated with inflammation, including rheumatoid arthritis, inflammatory bowel disease, vasculitis and several types of cancer. Moreover, IL-6 is important in the induction of hepatic acute-phase proteins for the trafficking of acute and chronic inflammatory cells, the differentiation of adaptive T-cell responses, and tissue regeneration and homeostatic regulation. Studies have investigated IL-6 biology using cell-bound IL-6 receptors expressed predominantly on hepatocytes and certain haematopoietic cells versus activation mediated by IL-6 and soluble IL-6 receptors via a second protein, gp130, which is expressed throughout the body. Advances in this research elucidating the differential effects of IL-6 activation provide important insights into the role of IL-6 in health and disease, as well as its potential as a therapeutic target. Knowledge of the basic biology of IL-6 and its signalling pathways can better inform both the research agenda for IL-6-based targeted therapies as well as the clinical use of strategies affecting IL-6-mediated inflammation. This Review covers novel, emerging aspects of the biology of IL-6, which might lead to more specific blockade of IL-6 signalling without compromising the protective function of this cytokine in the body's defence against infections.

Publication types

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

MeSH terms

  • Humans
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / physiology*
  • Rheumatic Diseases / drug therapy
  • Rheumatic Diseases / etiology*
  • Signal Transduction


  • Interleukin-6