Prostaglandin E2 and leukotriene B4 synthesis by peripheral leucocytes in alcoholics.
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.
Maxwell
W J
WJ
Department of Clinical Medicine, Trinity College and St. James's Hospital, Dublin, Ireland.
Keating
J J
JJ
Hogan
F P
FP
Kennedy
N P
NP
Keeling
P W
PW
D000328:Adult; D000437:Alcoholism / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D008108:Liver Diseases, Alcoholic / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism*
D007975:Leukotriene B4; D015232:Dinoprostone