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ToolsPage, Theresa H., Turner, Jeremy J. O., Brown, Anthony C., Timms, Emma M., Inglis, Julia J., Brennan, Fionula M., Foxwell, Brian M. J., Ray, Keith P. and Feldmann, Marc (2010) Nonsteroidal anti-inflammatory drugs increase TNF production in rheumatoid synovial membrane cultures and whole blood. Journal of Immunology, 185 (6). pp. 3694-3701. ISSN 0022-1767
Full text not available from this repository. (Request a copy)Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase activity and hence PG production. However, the ability of NSAIDs to ameliorate pain and tenderness does not prevent disease progression in rheumatoid arthritis, a disease whose pathogenesis is linked to the presence of proinflammatory cytokines, such as TNF-α. To understand this observation, we have examined the effect of NSAIDs on the production of clinically validated proinflammatory cytokines. We show that a variety of NSAIDs superinduce production of TNF from human peripheral blood monocytes and rheumatoid synovial membrane cultures. A randomized, double-blinded, crossover, placebo-controlled trial in healthy human volunteers also revealed that the NSAID drug celecoxib increased LPS-induced TNF production in whole blood. NSAID-mediated increases in TNF are reversed by either the addition of exogenous PGE2 or by a PGE2 EP2 receptor agonist, revealing that PGE2 signaling via its EP2 receptor provides a valuable mechanism for controlling excess TNF production. Thus, by reducing the level of PGE2, NSAIDs can increase TNF production and may exacerbate the proinflammatory environment both within the rheumatoid arthritis joint and the systemic environment.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit |
| Depositing User: | Rhiannon Harvey |
| Date Deposited: | 20 Apr 2011 12:03 |
| Last Modified: | 15 Jun 2023 15:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/29710 |
| DOI: | 10.4049/jimmunol.1000906 |
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