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ISRN Immunology
Volume 2012 (2012), Article ID 652739, 15 pages
http://dx.doi.org/10.5402/2012/652739
Review Article

What Have We Learned about the Pathogenesis of Rheumatoid Arthritis from TNF-Targeted Therapy?

Kennedy Institute of Rheumatology, University of Oxford, 65 Aspenlea Road, London W6 8LH, UK

Received 15 August 2012; Accepted 6 September 2012

Academic Editors: C. Baecher-Allan, B. Sawitzki, and S. Seki

Copyright © 2012 Richard O. Williams. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Studies of cytokine regulation in rheumatoid arthritis led to the development of TNFα inhibitors which are now used for a number of indications, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, and ankylosing spondylitis. The widespread use of biologics in the clinic offers unique opportunities for probing disease pathogenesis and this paper provides an overview of rheumatoid arthritis, with a particular emphasis on the impact of anti-TNFα therapy on pathogenetic mechanisms. An overview is also provided on the most commonly used animal models that mimic RA, including adjuvant-induced arthritis, collagen-induced arthritis, TNFα-transgenic mice, and the K/BxN and SKG models. These models have led to significant discoveries relating to the importance of pro-inflammatory cytokines in the pathogenesis of rheumatoid arthritis, resulting from disregulation of the normally finely tuned balance of pro- and anti-inflammatory cytokine signalling. In addition, experimental evidence is discussed suggesting how genetic and environmental factors can contribute to disease susceptibility. The role of effector and regulatory T cells is discussed in the light of the relatively disappointing therapeutic effects of T cell modifying agents such as anti-CD4 antibody and cyclosporin. It is concluded that comprehensive analyses of mechanisms of action of biologics and other drugs entering the clinic will be essential to optimise therapy, with the ultimate aim of providing a cure.