Skip Navigation



Rheumatology Advance Access published online on October 23, 2009
Rheumatology, doi:10.1093/rheumatology/kep329
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Dayer, J.-M.
Right arrow Articles by Choy, E.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dayer, J.-M.
Right arrow Articles by Choy, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author(s) 2009. Published by Oxford University Press on behalf of The British Society for Rheumatology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Review

Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor

Jean-Michel Dayer1 and Ernest Choy2

1Faculty of Medicine, Centre Médical Universitaire, Geneva, Switzerland and 2Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department of Rheumatology, King's College London, Weston Education Centre, London, UK.

Correspondence to: Ernest Choy, Sir Alfred Baring Garrod Clinical Trials Unit, Academic Department of Rheumatology, King's College London, Weston Education Centre, Cutcombe Road, London SE5 9RJ, UK. E-mail: ernest.choy{at}kcl.ac.uk


  Abstract

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.

KEY WORDS: Interleukin-6, Rheumatoid arthritis, Trans-signalling, Joint destruction, Systemic effects, Immune response, Receptor inhibition

Submitted 19 June 2009; revised version accepted 14 September 2009.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.