Involvement of leukotriene B4 in zymosan-induced rat pleurisy: inhibition of leukocyte infiltration by the 5-lipoxygenase inhibitor T-0757.

The role of leukotriene B4 (LTB4) in leukocyte infiltration in zymosan-induced rat pleurisy was investigated by studying the effects of 5-lipoxygenase inhibitors, T-0757 and AA-861, and a cyclooxygenase inhibitor, indomethacin, on leukocyte infiltration and LTB4 levels in the inflammatory exudate of rat pleurisy induced by intrapleural injection of zymosan (20 mg/rat). T-0757 and AA-861 inhibited the infiltration of leukocytes, mainly neutrophils, 3 h after injection of zymosan at a dose of 100 mg/kg, p.o., but indomethacin did not do so at a dose of 5 mg/kg, p.o. LTB4 was detected in the exudate 1 h after zymosan injection, and its level peaked at 3 h (45.4 +/- 8.6 ng/rat) and decreased thereafter. These LTB4 levels were depressed by T-0757 and AA-861 in a dose-dependent manner. T-0757 completely prevented LTB4 production at a dose of 100 mg/kg. These observations suggest that the inhibition of leukocyte infiltration is mediated by the inhibition of LTB4 production, and that LTB4 is one of the main chemical mediators of leukocyte infiltration in zymosan-induced rat pleurisy.