EFFECTS OF SA6541, A LEUKOTRIENE A(4) HYDROLASE INHIBITOR, AND INDOMETHACIN ON CARRAGEENAN-INDUCED MURINE DERMATITIS

We investigated the effects of )-N-[(2S)-3-mercapto-2-methylpropionyl] -L-cysteine (SA6541), a potent leukotriene A(4) hydrolase inhibitor, o n early phase of carrageenan-induced dermatitis model. Carrageenan inj ection induced edema and neutrophil influx in the mouse ear. SA6541 in hibited edema formation and neutrophil influx. SA6541 also inhibited l eukotriene B-4 production but not prostaglandin E-2 production in the mouse ear. On the other hand, indomethacin inhibited edema formation b ut not neutrophil influx. Indomethacin also inhibited prostaglandin E- 2 production but not leukotriene B-4 production. Combination therapy w ith SA6541 and indomethacin strongly inhibited edema formation in comp arison with treatment with either agent alone. These results suggest t hat leukotriene B-4 may be important in the pathogenesis of dermatitis . (C) 1998 Elsevier Science B.V.