T-CELL ACTIVATION, EXPRESSION OF ADHESION MOLECULES AND RESPONSE TO ETHANOL IN ALCOHOLIC CIRRHOSIS

Abnormal immune function is a well-recognized feature in patients with alcoholic cirrhosis. It may contribute to the pathogenesis of the dis ease and to the clinical consequences. Nevertheless, a potential role of ethanol to elicit immune disturbances in patients is still unclear. To further examine the immune mechanisms which potentially are involv ed in alcoholic cirrhosis and the relationship to ethanol, we have det ermined the expression of surface antigens CD4, CD8, and of adhesion m olecules CD25, LFA-1, ICAM-1 and LFA-3 in patients and in response to stimulation with OKT-3, IL-2 and with ethanol in vitro. In addition, w e quantified the production of IL-2, TNF-alpha and IFN-gamma by lympho cytes of alcoholic cirrhosis patients compared to controls. Lymphocyte s from patients showed increased basal and stimulated expression of CD 4, CD25, LFA-1, ICAM-1 and LFA-3 molecules and increased TNF-alpha pro duction in comparison to controls. When lymphocytes from patients were co-cultured with ethanol, the overexpression of activation markers an d TNF-alpha production was similar to that obtained with mitogens. In contrast, a predominant suppressive effect of ethanol was observed in lymphocytes from controls. Our study underlines the importance of a ch ronic state of immune activation in alcoholic cirrhosis. The data furt her suggest a role of ethanol to stimulate immune response and to be d irectly involved in the development of disease.