INTERCELLULAR-ADHESION MOLECULE-1 EXPRESSION IN EXPERIMENTAL ALCOHOLIC LIVER-DISEASE - RELATIONSHIP TO ENDOTOXEMIA AND TNF-ALPHA MESSENGER-RNA

We used the intragastric feeding rat model for alcoholic liver disease to evaluate the relationship among intercellular adhesion molecule-1 (ICAM-1) expression, tumor necrosis factor-alpha (TNF-alpha), plasma e ndotoxin, and inflammatory changes in the liver. Rats were fed differe nt dietary fats (saturated fat, corn oil, and fish oil) with ethanol; control rats were fed isocaloric amounts of dextrose instead of ethano l. At sacrifice the following were evaluated: liver pathologic changes , TNF-alpha mRNA by reverse transcription-PCR, plasma endotoxin, and I CAM-1 by immunohistochemistry and immunoblot analysis. Upregulation of ICAM-1 in endothelial lining cells in central and portal veins was ob served in rats showing evidence of pathologic changes. Rats fed fish o il and ethanol, which exhibited the most severe inflammation, also sho wed hepatocyte ICAM-1 staining. The presence of ICAM-1 staining, in ge neral, correlated with the level of TNF-alpha mRNA expression and plas ma endotoxin levels. Upregulation of ICAM-1 in rats fed ethanol may co ntribute to the inflammatory changes seen in this model. The associati on between ICAM-1 upregulation and endotoxin and TNF-alpha mRNA sugges ts a role for these mediators in the inflammatory process in alcoholic liver injury. (C) 1995 Academic Press, Inc.