Increased tumor necrosis factor production by monocytes in alcoholic hepatitis.
Tumor necrosis factor is a cytokine that mediates many of the biologic actions of endotoxin. Recent studies have shown that tumor necrosis factor administration may cause liver injury and that tumor necrosis factor may mediate the lethality of the hepatotoxin galactosamine. One of the most potent inducers of tumor necrosis factor production is endotoxin. Because patients with alcoholic liver disease frequently have endotoxemia and because many of the clinical manifestations of alcoholic hepatitis are known biologic actions of tumor necrosis factor, we thought it would be important to evaluate tumor necrosis factor activity in patients with alcoholic hepatitis. Basal and lipopolysaccharide-stimulated tumor necrosis factor release from peripheral blood monocytes, a major source of tumor necrosis factor production, was determined in 16 patients with alcoholic hepatitis and 16 healthy volunteers. Eight of 16 alcoholic hepatitis patients and only two of 16 healthy volunteers had detectable spontaneous tumor necrosis factor activity (p less than 0.05). After lipopolysaccharide stimulation, mean monocyte tumor necrosis factor release from alcoholic hepatitis patients was significantly increased to over twice that of healthy controls (25.3 +/- 3.7 vs. 10.9 +/- 2.4 units per ml, p less than 0.005). We conclude that monocytes from alcoholic hepatitis patients have significantly increased spontaneous and lipopolysaccharide-stimulated tumor necrosis factor release compared to monocytes from healthy volunteers. We suggest that some of the metabolic abnormalities and possibly some of the liver injury of alcoholic hepatitis may be due to enhanced tumor necrosis factor production.
McClain
C J
CJ
Department of Medicine, University of Kentucky Medical Center, Lexington 40536-0084.
Cohen
D A
DA
D000328:Adult; D006519:Hepatitis, Alcoholic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha