Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor

Rheumatology (Oxford). 2010 Jan;49(1):15-24. doi: 10.1093/rheumatology/kep329. Epub 2009 Oct 23.


RA is a chronic, debilitating disease in which articular inflammation and joint destruction are accompanied by systemic manifestations including anaemia, fatigue and osteoporosis. IL-6 is expressed abundantly in the SF of RA patients and is thought to mediate many of the local and systemic effects of this disease. Unlike a number of other cytokines, IL-6 can activate cells through both membrane-bound (IL-6R) and soluble receptors (sIL-6R), thus widening the number of cell types responsive to this cytokine. Indeed, trans-signalling, where IL-6 binds to the sIL-6R, homodimerizes with glycoprotein 130 subunits and induces signal transduction, has been found to play a key role in acute and chronic inflammation. Elevated levels of IL-6 and sIL-6R in the SF of RA patients can increase the risk of joint destruction and, at the joint level, IL-6/sIL-6R can stimulate pannus development through increased VEGF expression and increase bone resorption as a result of osteoclastogenesis. Systemic effects of IL-6, albeit through conventional or trans-signalling, include regulation of acute-phase protein synthesis, as well as hepcidin production and stimulation of the hypothalamo-pituitary-adrenal axis, the latter two actions potentially leading to anaemia and fatigue, respectively. This review aims to provide an insight into the biological effects of IL-6 in RA, examining how IL-6 can induce the articular and systemic effects of this disease.

Publication types

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

MeSH terms

  • Acute Disease
  • Adaptive Immunity
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology
  • Bone Resorption / immunology
  • Chronic Disease
  • Extracellular Matrix / metabolism
  • Humans
  • Interleukin-6 / immunology*
  • Interleukin-6 / metabolism
  • Receptors, Interleukin-6 / metabolism*
  • Signal Transduction / immunology


  • Interleukin-6
  • Receptors, Interleukin-6