Differential contribution of R and S isomers in ketoprofen anti-inflammatory activity: role of cytokine modulation

Among nonsteroidal anti-inflammatory drugs (NSAIDs), 2-arylpropionic acids exist as a racemic mixture of its enantiomeric forms, with S-enantiomers primarily responsible for inhibition of prostaglandin synthesis and of inflammatory events. The aim of this study was to compare the anti-inflammatory e...

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Bibliographic Details
Published in:The Journal of pharmacology and experimental therapeutics 1998-12, Vol.287 (3), p.969
Main Authors: Ghezzi, P, Melillo, G, Meazza, C, Sacco, S, Pellegrini, L, Asti, C, Porzio, S, Marullo, A, Sabbatini, V, Caselli, G, Bertini, R
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Carrageenan
Cytokines - biosynthesis
Dinoprostone - analysis
Edema - blood
Edema - chemically induced
Edema - prevention & control
Guinea Pigs
Hyperalgesia - blood
Hyperalgesia - chemically induced
Hyperalgesia - prevention & control
Ketoprofen - pharmacology
Lipopolysaccharides
Male
Stereoisomerism
Tumor Necrosis Factor-alpha - analysis
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Summary:Among nonsteroidal anti-inflammatory drugs (NSAIDs), 2-arylpropionic acids exist as a racemic mixture of its enantiomeric forms, with S-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- and S-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.
ISSN:0022-3565