DECREASED TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-ALPHA PRODUCTION FROM INTRAHEPATIC MONONUCLEAR-CELLS IN CHRONIC ETHANOL-CONSUMPTIONAND UP-REGULATION BY ENDOTOXIN

The relationship between the changes in liver pathology and the produc tion of interleukin (IL)-1 alpha, IL-6, and tumor necrosis factor-alph a (TNF-alpha) by intrahepatic mononuclear cells was studied in rats fe d alcohol and subsequently exposed to lipopolysaccharide (LPS), Rats w ere fed 40% ethanol in drinking water, whereas control rats were provi ded with a chow diet with isocaloric or 2% sucrose drinking solutions for up to 20 weeks, Decreased IL-1 alpha and TNF-alpha production in 2 4-hr culture supernatants of mononuclear cells isolated from liver per fusate was detected while IL-6 remained unchanged over 20 weeks, When animals were injected with LPS (1.0 mu g/kg body weight), there was a fi-fold rise in ALT levels in the ethanol-fed group, but not in contro l groups, Increased IL-6 and TNF-alpha levels in the serum and superna tant of cultured intrahepatic mononuclear cells stimulated with or wit hout LPS or concanavalin A was observed, There was a correlation betwe en levels of ALT and TNF-alpha, but not IL-6, T cells and Kupffer cell s were the major source of TNF-alpha in culture supernatants of hepati c perfusate mononuclear cells from ethanol-consuming rats injected LPS , In addition, pathological liver injury was evident, which suggests a pathogenic role for TNF-alpha in alcohol-induced liver disease.