Suppression of Tumor Necrosis Factor Production by Alcohol in Lipopolysaccharide‐Stimulated Culture Article

Nair, MPN, Schwartz, SA, Kronfol, ZA et al. (1994). Suppression of Tumor Necrosis Factor Production by Alcohol in Lipopolysaccharide‐Stimulated Culture . ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 18(3), 602-607. 10.1111/j.1530-0277.1994.tb00917.x

cited authors

  • Nair, MPN; Schwartz, SA; Kronfol, ZA; Hill, EM; Sweet, AM; Greden, JF

authors

abstract

  • 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 ficollhypaque separated total mononuclear cells (1 × 106/ml) were cultured with different concentrations of either ethanol or acetaldehyde in the presence or absence of LPS for 4 hr at 37°C. Plasma samples and culture supernatants were assayed for TNF levels in a bioassay using a TNF‐sensitive WEHl 164 sub‐clone 13 cell line. LPS at 10 μg/ml produced a maximal level of TNF compared with lower (1 μg/ml) or higher concentration (50 μg/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‐inducted 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‐α antibodies significantly neutralized the LPS‐induced TNF that suggests that blood monocytes may be the primary source of TNF production. Further, significant correlation between TNF production and monocyte numbers was observed. Acetaldehyde one of the primary metabolites of alcohol, did not suppress the LPS‐induced TNF production by whole blood. These studies suggest that alcohol‐induced inhibition of TNF may be one of the mechanisms for immunosuppression in alcoholic patients. Copyright © 1994, Wiley Blackwell. All rights reserved

publication date

  • January 1, 1994

published in

Digital Object Identifier (DOI)

start page

  • 602

end page

  • 607

volume

  • 18

issue

  • 3