Maxwell W J, Keating J J, Hogan F P, Kennedy N P, Keeling P W
Department of Clinical Medicine, Trinity College and St. James's Hospital, Dublin, Ireland.
Gut. 1989 Sep;30(9):1270-4. doi: 10.1136/gut.30.9.1270.
Alcohol inhibits phospholipase (PL) activity in a number of animal models. We have therefore measured prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), liberated by stimulated peripheral blood mononuclear cells (PBMC) and neutrophils respectively in chronic alcoholics and in control subjects. Peripheral blood mononuclear cells from alcoholics produced less PGE2 (p less than 0.01) and neutrophils produced less LTB4 (p less than 0.025). Reduced PGE2 production by PBMC of alcoholics was corrected by the addition of exogenous arachidonic acid (p less than 0.005) whilst neutrophil LTB4 production remained lower in the alcoholics (p less than 0.01). Percutaneous liver biopsies were undertaken in the 20 alcoholics having abnormal liver function tests. Prostaglandin E2 biosynthesis was lower in PBMC from patients with alcoholic hepatitis than with alcoholic cirrhosis (p less than 0.05). Analysis of PBMC fatty acid composition demonstrated that endogenous arachidonate and linoleate contents were not significantly different in alcoholics and controls. Cells from controls and alcoholics were incubated with 0, 50 and 150 mmol/l ethanol for two hours but there was no alteration in PGE2 or LTB4 biosynthesis. In summary, we found reduced eicosanoid production by peripheral leucocytes in alcoholics, supporting the hypothesis that chronic alcohol consumption either inhibits membrane bound phospholipase activity or enhances, alternatively, catabolism of eicosanoids. This phenomenon is more marked in alcoholic patients with hepatitis than in those with cirrhosis alone.
在许多动物模型中，酒精会抑制磷脂酶（PL）的活性。因此，我们测定了慢性酒精中毒患者和对照受试者外周血单个核细胞（PBMC）和中性粒细胞分别释放的前列腺素E2（PGE2）和白三烯B4（LTB4）。酒精中毒患者的外周血单个核细胞产生的PGE2较少（p<0.01），中性粒细胞产生的LTB4较少（p<0.025）。添加外源性花生四烯酸可纠正酒精中毒患者PBMC中PGE2产生的减少（p<0.005），而酒精中毒患者中性粒细胞LTB4的产生仍然较低（p<0.01）。对20例肝功能检查异常的酒精中毒患者进行了经皮肝活检。酒精性肝炎患者PBMC中的前列腺素E2生物合成低于酒精性肝硬化患者（p<0.05）。PBMC脂肪酸组成分析表明，酒精中毒患者和对照组的内源性花生四烯酸和亚油酸含量无显著差异。将对照组和酒精中毒患者的细胞分别与0、50和150 mmol/l乙醇孵育两小时，但PGE2或LTB4的生物合成没有改变。总之，我们发现酒精中毒患者外周白细胞产生的类花生酸减少，支持了慢性饮酒要么抑制膜结合磷脂酶活性，要么增强类花生酸分解代谢的假说。这种现象在酒精性肝炎患者中比仅患有肝硬化的患者更为明显。
