Abstract
Among nonsteroidal anti-inflammatory drugs (NSAIDs), 2-arylpropionic acids exist as a racemic mixture of its enantiomeric forms, withS-enantiomers primarily responsible for inhibition of prostaglandin synthesis and of inflammatory events. The aim of this study was to compare the anti-inflammatory effects of R- andS-ketoprofen in vitro and in vivo.S-Ketoprofen efficiently inhibited carrageenan-induced edema formation, but it could also amplify the LPS-induced production of the inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1), in close correlation with its ability to inhibit prostaglandin synthesis. Because these inflammatory cytokines are among the factors involved in carrageenan-induced inflammation and also are possibly involved in gastric damage, enhanced cytokine production could partially mask the analgesic effect of S-ketoprofen, and it can be associated with the clinical evidence of its gastric toxicity. On the other hand, R-ketoprofen contributes to the overall activity of the racemate, by playing the main role in ketoprofen-induced analgesia. Unlike the S-isomer,R-ketoprofen did not induce a significant increase of cytokine production even at cyclooxygenase-blocking concentrations. It is concluded that the R-isomer directly contributes to the anti-inflammatory effects of ketoprofen, being more analgesic, and because it does not amplify inflammatory cytokine production.
Footnotes
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Send reprint requests to: Dr. Riccardo Bertini, DompéS.p.A., via Campo di Pile, 67100 L’Aquila, Italy.
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↵1 This work was partially supported by the contract “Programma Nazionale di Ricerca e Formazione sui Farmaci (seconda fase), Tema 4,” granted by the Italian Ministry of University and Scientific and Technological Research.
- Abbreviations:
- NSAID
- nonsteroidal anti-inflammatory drug
- PGE2
- prostaglandin E2
- LPS
- bacterial endotoxin
- TNF
- tumor necrosis factor
- IL
- interleukin
- Received December 9, 1997.
- Accepted July 6, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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