CHRONIC ETHANOL INGESTION IMPAIRS ALVEOLAR TYPE-II CELL GLUTATHIONE HOMEOSTASIS AND FUNCTION AND PREDISPOSES TO ENDOTOXIN-MEDIATED ACUTE EDEMATOUS LUNG INJURY IN RATS

Chronic alcohol abuse increases the incidence and mortality of the acu te respiratory distress syndrome (ARDS) in septic patients. To examine a potential mechanism, we hypothesized that ethanol ingestion predisp oses to sepsis-mediated acute lung injury by decreasing alveolar type II cell glutathione homeostasis and function. Lungs isolated from rats fed ethanol(20% in water for greater than or equal to 3 wk), compared with lungs from control-fed rats, had greater (P < 0.05) edematous in jury (reflected by nonhydrostatic weight gain) after endotoxin (2 mg/k g intraperitoneally) and subsequent perfusion ex vivo with n-formylmet hionylleucylphenylalanine (fMLP, 10(-7) M). Ethanol ingestion decrease d (P < 0.05) glutathione levels in the plasma, lung tissue, and lung l avage fluid, and increased (P < 0.05) oxidized glutathione levels in t he lung lavage fluid, Furthermore, ethanol ingestion decreased type II cell glutathione content by 95% (P < 0.05), decreased (P ( 0.05) type II cell surfactant synthesis and secretion, and decreased (P < 0.05) type II cell viability, in vitro, Finally, treatment with the glutathi one precursors S-adenosyl-L-methionine and N-acetylcysteine in the fin al week of ethanol ingestion significantly reduced lung edema during p erfusion ex vivo, We conclude that ethanol ingestion in rats alters al veolar type II cell glutathione levels and function, thereby predispos ing the lung to acute edematous injury after endotoxemia, We speculate that chronic alcohol abuse in humans predisposes to ARDS through simi lar mechanisms.