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

Abstract

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 B₄ (LTB₄) and leukotriene C₄ (LTC₄) generation were dose-dependently impaired by ethanol. No significant difference in the levels of the ω-oxidized metabolites was observed. However, the total LTB₄ production (LTB₄ plus ω-oxidized metabolites) was significantly decreased in the samples treated with ethanol. Furthermore, ethanol also modulated LTB₄-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 LTB₄ 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 LTB₄-induced functional responses were inhibited.

Key Words:

• alcohol
• calcium mobilization
• inflammation
• oxidative metabolism
• PMNL