Increased peripheral mononuclear cells expression of adhesion molecules in alcoholic cirrhosis: its relation to immune activation.

BACKGROUND/AIMS: Cell adhesion phenomena are relevant in the immune mechanisms leading to organ damage in various diseases. Patients with alcoholic cirrhosis present with immune alterations that include findings of immunodeficiency and indications of an activated immune response. METHODS: In 37 patients with alcoholic cirrhosis we have determined the expression of surface antigens and adhesion molecules on peripheral lymphocytes and monocytes, serum levels of immunoglobulins, circulating cytokines, namely tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta, serum soluble intercellular adhesion molecule and neopterin. RESULTS: In patients, we found an increased expression of several adhesion molecules ICAM-1, LFA-3 and MAC-1 in lymphocytes, LFA-3 in monocytes and surface activation markers CD71 and DR in lymphocytes, as well as increased concentrations of the serum parameters measured: IgA, IgG, IgM, interleukin-1 beta, interleukin-6, tumor necrosis factor-alpha, soluble ICAM-1 and neopterin, in comparison with controls. CONCLUSIONS: The enhancement of the adhesion phenomena in circulating mononuclear cells of patients with cirrhosis correlates to the severity of the disease and is related to other parameters of immune activation.

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 disease 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 involved in alcoholic cirrhosis and the relationship to ethanol, we have determined the expression of surface antigens CD4, CD8, and of adhesion molecules 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, we quantified the production of IL-2, TNF-alpha and IFN-gamma by lymphocytes of alcoholic cirrhosis patients compared to controls. Lymphocytes from patients showed increased basal and stimulated expression of CD4, CD25, LFA-1, ICAM-1 and LFA-3 molecules and increased TNF-alpha production in comparison to controls. When lymphocytes from patients were co-cultured with ethanol, the overexpression of activation markers and 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 chronic state of immune activation in alcoholic cirrhosis. The data further suggest a role of ethanol to stimulate immune response and to be directly involved in the development of disease.