The effects of acute and chronic alcoholism on tumor necrosis factor and the inflammatory response.
Ethanol intoxication has been shown to suppress selected functions of the immune system, thereby compromising host defenses against bacterial infections. Because the macrophage secretory protein, tumor necrosis factor (TNF), plays a central role in the inflammatory cascade, the effect of acute and chronic alcoholism on lipopolysaccharide (LPS)-induced TNF activity was studied. Saline or ethanol was given intraperitoneally to normal or chronic alcoholic rats followed 30 min later by either intravenous or intratracheal LPS. Intravenous LPS caused a substantial increase in serum TNF at 90 min in both normal and chronic alcoholic rats. In marked contrast, peak serum TNF levels were significantly suppressed in normal and chronic alcoholic rats given an acute injection of ethanol. When LPS was instilled intratracheally into normal rats, high levels of TNF appeared in the bronchoalveolar lavage fluid. Similar levels of TNF were found in chronic alcoholic rats after intratracheal LPS. However, acute ethanol intoxication significantly inhibited LPS-induced TNF in bronchoalveolar lavage fluid. In a similar manner, acute ethanol intoxication, but not chronic alcohol consumption, markedly inhibited both systemic and intrapulmonary polymorphonuclear leukocyte aggregation in response to either intravenous or intratracheal LPS. Alcohol-induced inhibition of TNF is a potential mechanism of the antiinflammatory effects of ethanol.
Nelson
S
S
Department of Pulmonary/Critical Care Medicine, Louisiana State University Medical Center, New Orleans 70112.
Bagby
G J
GJ
Bainton
B G
BG
Summer
W R
WR
D000435:Alcoholic Intoxication / Q000503:physiopathology*; D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D004926:Escherichia coli; D000431:Ethanol / Q000097:blood; D007249:Inflammation; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008264:Macrophages / Q000166:cytology; D008297:Male; D009504:Neutrophils / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol