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.
Santos-Perez
J L
JL
Department of Biochemistry, University Hospital of Granada, Spain.
Diez-Ruiz
A
A
Luna-Casado
L
L
Soto-Mas
J A
JA
Wachter
H
H
Fuchs
D
D
Gutierrez-Gea
F
F
D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008104:Liver Cirrhosis, Alcoholic / Q000503:physiopathology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D016207:Cytokines; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol