TY - JOUR T1 - Differential Contribution of <em>R</em> and <em>S</em>Isomers in Ketoprofen Anti-inflammatory Activity: Role of Cytokine Modulation JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 969 LP - 974 VL - 287 IS - 3 AU - Pietro Ghezzi AU - Gabriella Melillo AU - Cristina Meazza AU - Silvano Sacco AU - Luigi Pellegrini AU - Cinzia Asti AU - Stefano Porzio AU - Antonello Marullo AU - Vilma Sabbatini AU - Gianfranco Caselli AU - Riccardo Bertini Y1 - 1998/12/01 UR - http://jpet.aspetjournals.org/content/287/3/969.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -