Decreased tumor necrosis factor-alpha and interleukin-1alpha production from intrahepatic mononuclear cells in chronic ethanol consumption and upregulation by endotoxin.
The relationship between the changes in liver pathology and the production of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) by intrahepatic mononuclear cells was studied in rats fed alcohol and subsequently exposed to lipopolysaccharide (LPS). Rats were fed 40% ethanol in drinking water, whereas control rats were provided with a chow diet with isocaloric or 2% sucrose drinking solutions for up to 20 weeks. Decreased IL-1alpha and TNF-alpha production in 24-hr culture supernatants of mononuclear cells isolated from liver perfusate was detected while IL-6 remained unchanged over 20 weeks. When animals were injected with LPS (1.0 microg/kg body weight), there was a 5-fold rise in ALT levels in the ethanol-fed group, but not in control groups. Increased IL-6 and TNF-alpha levels in the serum and supernatant of cultured intrahepatic mononuclear cells stimulated with or without LPS or concanavalin A was observed. There was a correlation between levels of ALT and TNF-alpha, but not IL-6. T cells and Kupffer cells were the major source of TNF-alpha in culture supernatants of hepatic 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.
Batey
R
R
Department of Gastroenterology, John Hunter Hospital, Newcastle, NSW, Australia.
Cao
Q
Q
Madsen
G
G
Pang
G
G
Russell
A
A
Clancy
R
R
D000818:Animals; D019446:Endotoxemia / Q000276:immunology*; D005260:Female; D007375:Interleukin-1 / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D007728:Kupffer Cells / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008108:Liver Diseases, Alcoholic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha