Effects of nimesulide, a preferential cyclooxygenase-2 inhibitor, on carrageenan-induced pleurisy and stress-induced gastric lesions in rats

Abstract

Intrapleural injection of carrageenan in rats increased prostaglandin E 2 (PGE 2) production and induced newly synthesized cyclooxygenase-2 (COX-2) in pleural exudate cells without affecting COX-1 levels. Nimesulide, a preferential inhibitor of COX-2, reduced pleural PGE 2 production and was almost as active as indomethacin and 10 times more active than ibuprofen. Only COX-1, and no COX-2, was detected in gastric mucosal cells, and PGE 2 concentration of gastric mucosa was significantly decreased by indomethacin and ibuprofen. The decrease in gastric PGE 2 production induced by indomethacin and ibuprofen was enhanced in stressed rats, resulting in aggravation of stress-induced gastric lesions at anti-inflammatory doses. However, nimesulide did not produce stress-induced gastric lesions even at 30 times the anti-inflammatory dose. This supports the hypothesis that inhibition of COX-1 causes unwanted side effects and inhibition of COX-2 produces anti-inflammatory effects.