Enhanced urinary excretion of cysteinyl leukotrienes in patients with acute alcohol intoxication

Background & Aims: Leukotrienes are proinflammatory mediators. Ethanol inhi bits the catabolism of both cysteinyl leukotrienes (leukotriene E-4 [LTE4] and N-acetyl-LTE4) and leukotriene B-4 (LTB4) in hepatocytes, We examined t he metabolic derangement of leukotriene inactivation by ethanol in humans i n vivo. Methods: LTE4, N-acetyl-LTE4, LTB4, and 20-hydroxy-LTB4 were quanti fied in urine samples from 16 patients with acute alcohol intoxication (mea n blood ethanol, 75 mmol/L), In 9 healthy volunteers, urinary LTE4 was dete rmined before and after ethanol consumption (mean blood ethanol, 14 mmol/L) , Results: The excretion of LTE4 during alcohol intoxication was 286 compar ed with 36 nmol/mol creatinine in healthy subjects (P < 0.01); the correspo nding values for N-acetyl-LTE4 were 101 and 11 nmol/mol creatinine, respect ively (P < 0.001). This excretion of cysteinyl leukotrienes decreased when the blood ethanol concentration returned to normal. LTB4 and 20-hydroxy-LTB 4 were detectable only in patients with excessive blood ethanol concentrati ons (mean, 95 mmol/L), In healthy volunteers, LTE4 excretion increased 3-5 hours after ethanol consumption (mean peak concentration of 1.5 nmol/L comp ared with 0.5 nmol/L for basal values; P < 0.005), Conclusions: Ethanol at high concentration induces increased leukotriene excretion into urine. Thes e changes are consistent with inhibition of leukotriene catabolism and inac tivation induced by ethanol, as well as with a higher leukotriene formation caused by ethanol-induced endotoxemia.