IMR Press / FBL / Volume 10 / Issue 3 / DOI: 10.2741/1712

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


The toll-like receptor-nuclear factor κB pathway in rheumatoid arthritis

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1 Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, London, United Kingdom

Academic Editor: Joseph Holoshitz

Front. Biosci. (Landmark Ed) 2005, 10(3), 2478–2488;
Published: 1 September 2005
(This article belongs to the Special Issue The pathogenesis of rheumatoid arthritis)

The study of the role cytokines play in the pathogenesis of rheumatoid arthritis (RA) has provided a whole new range of targets for drug development. Many of them (e.g. TNF, IL-1, IL-6, IL-15 and IL-18) are already being targeted in the clinic with success using neutralizing monoclonal antibodies or soluble cytokine receptors. Targeting TNF, in particular, has shown great efficacy in controlling both the inflammation and structural damage of the joints, setting a new gold standard for the treatment of RA. However, what triggers the production of inflammatory cytokines such as TNF in RA remains to be determined. In this article, we review evidence suggesting that the transcription factor Nuclear Factor κB (NF-κB) is essential for the expression of both inflammatory cytokines and tissue destructive enzymes in RA. Also, we discuss whether Toll-like receptors (TLRs), major receptors involved in pathogen recognition and potent activators of the NF-κB pathway, are involved in triggering the inflammatory and joint destructive process in RA and whether they constitute sensible targets for monoclonal antibodies/soluble receptors and small molecule inhibitors. We conclude that although the TLR- NF-κB pathway offers ample opportunities for therapeutic intervention, future drugs to be approved will need to match or exceed the efficacy and safety of anti-TNF agents, with safety the most difficult aspect to predict.

Toll-like receptor
rheumatoid arthritis
IκB kinase
tumor necrosis factor
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