concanavalin-a and Hepatitis--Alcoholic

Recent work from our laboratory implicates T cells in the pathogenesis of alcoholic liver disease. We have studied the role of liver-associated T cells in acute hepatitis produced in control rats administered Concanavalin A (Con A) after adoptive transfer of T cells from alcohol-consuming animals.. Liver-associated T cells from ethanol-consuming rats were transferred via tail vein to nonethanol-consuming rats. They then received Con A (20 mg/kg body weight) intravenously. This produced a severe hepatitis. Serum was collected for the assay of alanine aminotransferase (ALT) and cytokines.. Hepatic necrosis was accompanied by an increase in plasma levels of ALT, interleukin-6, and tumor necrosis factor-alpha. These increases correlated with increased production of interleukin-6 and tumor necrosis factor-alpha in culture of liver-associated T cells stimulated or unstimulated with Con A. Immunohistology staining showed increased infiltration of inflammatory cells comprised of neutrophils and mononuclear cells, which included greater numbers of CD4+ T cells in the portal tract areas and around the central vein. Focal and lobular necrosis was seen with inflammatory cells in the necrotic area. Hepatocytes isolated from the liver showed increased apoptosis compared with rats that received liver-associated T cells from nonethanol-consuming rats. Injection of endotoxin LPS, in the same model, was associated with less hepatocyte injury indicating a distinct role for T cells as opposed to Kupffer cells in this model of liver disease.. Chronic ethanol consumption induces a lesion in a pool of liver-associated T cells which can mediate liver injury after polyclonal mitogen activation.

Topics: Alanine Transaminase; Animals; Apoptosis; Central Nervous System Depressants; Concanavalin A; Endotoxins; Ethanol; Female; Hepatitis, Alcoholic; Interleukin-6; Lipopolysaccharides; Mitogens; Rats; Rats, Wistar; T-Lymphocytes; Tumor Necrosis Factor-alpha

Concanavalin A-induced lymphocyte proliferation was studied in 25 patients with alcoholic hepatitis or compensated alcoholic cirrhosis. Nine alcoholics without evidence of liver disease were also evaluated. A nonlinear correlation equation, which was natural logarithmic, was applied to individual dose-response proliferation curves and permitted comparisons between patient groups and controls. The proliferative response in all patient groups was significantly lower when compared to healthy controls and was independent of the presence or absence of liver disease. This suggests that some changes in immune function observed in alcoholics may be linked to the direct effects of alcohol on the immune system rather than to the associated liver disease.

Topics: Alcoholism; Concanavalin A; Female; Hepatitis, Alcoholic; Humans; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Liver Function Tests; Lymphocyte Activation; Male