Enhanced secretion of prostaglandin E2 by tissue-fixed macrophages in colonic carcinoma.

Prostaglandin E2 (PGE2) secretion by peripheral blood and tissue-fixed macrophages from patients with colorectal carcinoma was assessed. There was no significant difference between PGE2 production by peripheral blood mononuclear cells between patients with colorectal carcinoma and normal controls. However, secretion of PGE2 by tissue-fixed macrophages from within the colorectal carcinomata in response to opsonised zymosan was significantly higher than in the uninvolved colonic tissue. PGE2 production by tissue-fixed macrophages from within colonic polyps was found to be normal. These results could not be explained on the basis of increased availability of substrate arachidonic acid since addition of excess arachidonic acid resulted in similar findings. The enhanced production of PGE2 correlated with Dukes staging but not the level of differentiation. The production of PGE2 from epithelial cells in response to ionophore A23187 was not significantly enhanced. Leukotriene B4 secretion by intestinal macrophages in response to opsonised zymosan was not significantly elevated in the colonic tumour tissue. Modulation of levels of prostaglandin production within colonic tumours may play a role in the rate of growth and vascularity of these tumours and in the regulation of the local immune response to malignancy.

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.