Therapeutic targets in rheumatoid arthritis: the interleukin-6 receptor

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 o...

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Bibliographic Details
Published in:Rheumatology (Oxford, England) England), 2010-01, Vol.49 (1), p.15-24
Main Authors: Dayer, Jean-Michel, Choy, Ernest
Format: Article
Language:English
Subjects:
Acute Disease
Adaptive Immunity
Arthritis, Rheumatoid - immunology
Arthritis, Rheumatoid - physiopathology
Biological and medical sciences
Bone Resorption - immunology
Chronic Disease
Diseases of the osteoarticular system
Extracellular Matrix - metabolism
Humans
Immune response
Inflammatory joint diseases
Interleukin-6
Interleukin-6 - immunology
Interleukin-6 - metabolism
Joint destruction
Medical sciences
Receptor inhibition
Receptors, Interleukin-6 - metabolism
Reviews
Rheumatoid arthritis
Signal Transduction - immunology
Systemic effects
Trans-signalling
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Summary: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.
ISSN:1462-0324
1462-0332
DOI:10.1093/rheumatology/kep329