INVOLVEMENT OF LEUKOTRIENE B₄ IN ZYMOSAN-INDUCED RAT PLEURISY : INHIBITION OF LEUKOCYTE INFILTRATION BY THE 5-LIPOXYGENASE INHIBITOR T-0757

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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 100mg/kg, p.o., but indomethacin did not do so at a dose of 5 mg/kg, p.o. LTB₄ was detected in the exudate 1h after zymosan injection, and its level peaked at 3h (45.4±8.6ng/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.