HEPATIC 60-KD HEAT-SHOCK PROTEIN RESPONSES IN ALCOHOLIC HEPATITIS

The precise mechanism of the pathogenesis of alcoholic hepatitis is un known, but immune involvement may perpetuate and exacerbate the proces s. Heat-shock proteins, normally protective, may be immunogenic and ha ve been shown to induce antibody formation in some inflammatory condit ions. Alcohol, cellular hypoxia and tumor necrosis factor, all involve d in alcoholic hepatitis, are potent inducers of heat-shock protein. I n this study, we sought 60-kD heat-shock protein in liver tissue with a murine monoclonal antibody and measured circulating antibody to 60-k D heat-shock protein on ELISA. Fourteen of 20 livers from patients wit h acute alcoholic hepatitis expressed 60-kD heat-shock protein in hepa tocyte cytoplasm in a diffuse pattern with superimposed clusters; othe r cell types were occasionally positive. Twelve of these patients had high-titer IgA 60-kD heat-shock protein antibody in serum. In contrast , 60-kD heat-shock protein was identified in only 2 of the 10 patients with alcoholic cirrhosis without hepatitis (p = 0.013). These two pat ients had severe liver disease, and one patient in this group was sero positive for IgA 60-kD heat-shock protein antibody. Eight alcoholic pa tients with fatty liver alone were negative for antigen, and all but o ne were negative for antibody. The 10 patients without liver damage we re negative for antigen and antibody. The findings that 60-kD heat-sho ck protein is present in liver tissue of patients with acute alcoholic liver damage and that circulating IgA 60-kD heat-shock protein antibo dy levels are increased may point to one pathogenetic mechanism underl ying development and progression of liver damage in alcoholic hepatiti s.