Ethanol affects leukotriene generation and leukotriene-induced functional responses in human polymorphonuclear granulocytes.

Since ethanol has been shown to inhibit the inflammatory response, we evaluated whether ethanol affected generation of leukotrienes in polymorphonuclear granulocytes (PMN) in vitro. Using the calcium ionophore A23187 as stimulus, the leukotriene B-4 (LTB(4)) and leukotriene C-4 (LTC(4)) generation were dose-dependently impaired by ethanol. No significant difference in the levels of the omega-oxidized metabolites was observed. However, the total LTB(4) production (LTB(4) plus omega-oxidized metabolites) was significantly decreased in the samples treated with ethanol. Furthermore, ethanol also modulated LTB(4)-induced functional responses. PMN aggregation, oxidative metabolism and elastase release were all inhibited in the presence of 1% ethanol (to 74 +/- 15%, 50 +/- 4% and 57 +/- 3% of controls, respectively). However, ethanol had no effect on intracellular calcium mobilization or on the change of the PMN membrane potential induced by either LTB(4) or A23187. Thus, a possible mechanism for the reduced functional PMN responses in the presence of ethanol might be impaired generation of leukotrienes, but it is conceivable that ethanol impairs also other steps of the stimulus response coupling since the LTB(4)-induced functional responses were inhibited.