Suppression of tumor necrosis factor production by alcohol in lipopolysaccharide-stimulated culture.
Many studies have shown that alcohol consumption is associated with alteration in immune responses and increased incidence of infection in the host. Tumor necrosis factor (TNF) is a potent soluble mediator of immunoregulation and inflammation, and plays a very important role in host's defenses against infection and tumor. We propose that one of the mechanisms of alcohol-mediated immunosuppression may be due to a defect in the synthesis and release of the TNF. To determine this, we studied the direct effect of alcohol on lipopolysaccharide (LPS)-induced TNF production by whole blood and total mononuclear cell from normal subjects. Aliquots of blood samples (1 ml) or ficoll-hypaque separated total mononuclear cells (1 x 10(6)/ml) were cultured with different concentrations of either ethanol or acetaldehyde in the presence or absence of LPS for 4 hr at 37 degrees C. Plasma samples and culture supernatants were assayed for TNF levels in a bioassay using a TNF-sensitive WEHI 164 subclone 13 cell line. LPS at 10 micrograms/ml produced a maximal level of TNF compared with lower (1 micrograms/ml) or higher concentration (50 micrograms/ml) of LPS. Kinetics studies showed that an incubation time of 4 hr with LPS produced a maximum level of TNF production by blood. Alcohol, as low as 0.1% concentration, produced significant suppression of LPS-induced TNF production by whole blood, whereas alcohol at 0.2 and 0.3% concentrations were required to produce a significant suppression of TNF production by separated mononuclear cells. Anti-TNF-alpha antibodies significantly neutralized the LPS-induced TNF that suggests that blood monocytes may be the primary source of TNF production.(ABSTRACT TRUNCATED AT 250 WORDS)
Nair
M P
MP
Department of Medicine, State University of New York at Buffalo 14203.
Schwartz
S A
SA
Kronfol
Z A
ZA
Hill
E M
EM
Sweet
A M
AM
Greden
J F
JF
D000328:Adult; D000437:Alcoholism / Q000276:immunology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000276:immunology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol