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

Madhavan P N Nair, Stanley A. Schwartz, Ziad Kronfol, Elizabeth M. Hill, Ann M. Sweet, John F. Greden

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)602-607
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume18
Issue number3
DOIs
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Tumor Necrosis Factor-alpha
Alcohols
Blood
Lipopolysaccharides
Acetaldehyde
Immunosuppression
Monocytes
Inflammation Mediators
Bioassay
Alcoholics
Metabolites
Infection
Alcohol Drinking
Biological Assay
Tumors
Ethanol
Cells
Plasmas
Cell Line
Defects

Keywords

  • Alcohol
  • Immunoregulation
  • Tumor Necrosis Factor

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

Suppression of Tumor Necrosis Factor Production by Alcohol in Lipopolysaccharide‐Stimulated Culture. / Nair, Madhavan P N; Schwartz, Stanley A.; Kronfol, Ziad; Hill, Elizabeth M.; Sweet, Ann M.; Greden, John F.

In: Alcoholism: Clinical and Experimental Research, Vol. 18, No. 3, 1994, p. 602-607.

Research output: Contribution to journalArticle

Nair, Madhavan P N ; Schwartz, Stanley A. ; Kronfol, Ziad ; Hill, Elizabeth M. ; Sweet, Ann M. ; Greden, John F. / Suppression of Tumor Necrosis Factor Production by Alcohol in Lipopolysaccharide‐Stimulated Culture. In: Alcoholism: Clinical and Experimental Research. 1994 ; Vol. 18, No. 3. pp. 602-607.
@article{c5af15217d9845a1a3f921e94e6bb5d7,
title = "Suppression of Tumor Necrosis Factor Production by Alcohol in Lipopolysaccharide‐Stimulated Culture",
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.",
keywords = "Alcohol, Immunoregulation, Tumor Necrosis Factor",
author = "Nair, {Madhavan P N} and Schwartz, {Stanley A.} and Ziad Kronfol and Hill, {Elizabeth M.} and Sweet, {Ann M.} and Greden, {John F.}",
year = "1994",
doi = "10.1111/j.1530-0277.1994.tb00917.x",
language = "English",
volume = "18",
pages = "602--607",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Suppression of Tumor Necrosis Factor Production by Alcohol in Lipopolysaccharide‐Stimulated Culture

AU - Nair, Madhavan P N

AU - Schwartz, Stanley A.

AU - Kronfol, Ziad

AU - Hill, Elizabeth M.

AU - Sweet, Ann M.

AU - Greden, John F.

PY - 1994

Y1 - 1994

N2 - 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.

AB - 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.

KW - Alcohol

KW - Immunoregulation

KW - Tumor Necrosis Factor

UR - http://www.scopus.com/inward/record.url?scp=0028365752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028365752&partnerID=8YFLogxK

U2 - 10.1111/j.1530-0277.1994.tb00917.x

DO - 10.1111/j.1530-0277.1994.tb00917.x

M3 - Article

VL - 18

SP - 602

EP - 607

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 3

ER -