Regulation of monocyte interleukin-12 production by acute alcohol: A role for inhibition by interleukin-10

Linda Girouard, Pranoti Mandrekar, Donna Catalano, Gyongyi Szabo

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Acute ethanol treatment results in decreased antigen presentation capacity (Th1-type immunity) and elevated interleukin IL-10 (Th2 cytokine) production in human monocytes. Monocytes can contribute to both Th1 (IL-12) and Th2 (IL-10) immune responses via production of IL-12 and IL-10, respectively. Thus, we tested the hypothesis that acute alcohol treatment might affect Th1/Th2 immune balance by altering monocyte production of IL-12 and IL-10. Neither acute ethanol treatment alone (25 to 100 mM) nor its combination with a bacterial challenge Staphylococcal enterotoxin B (SEB) induced IL-12 production in isolated blood monocytes. In contrast, the same physiological alcohol concentrations increased monocyte IL-10 levels, suggesting that ethanol can induce a dysbalance of monocyte-derived mediator production at the expense of Th1 cytokines. However, we found that monocyte activation with interferon-γ (IFN-γ) can prevent the preferential IL-10 induction by ethanol. IFN-γ (100 units/ml) inhibited monocyte IL-10 production whether induced by 1 μg/ml of lipopolysaccharide (p < 0.01), 1 μg/ml of SEB (p < 0.02), or a combination of bacterial stimulation + ethanol (lipopolysaccharide: p < 0.01). Furthermore, decreased IL-10 was concomitant to an increase in IL-12 production in IFN-γ-treated monocytes. Moreover, acute ethanol treatment augmented IL-12 production in IFN-γ-treated monocytes in response to SEB stimulation (25 mM ethanol, p < 0.01; 100 mM ethanol, p < 0.01). Experiments with anti-IL-10 neutralizing antibody show that ethanol may prevent monocyte IL-12 induction via IL-10. These results suggest that inhibition of ethanol-induced IL-10 production by IFN-γ treatment is permissive for IL-12 induction by alcohol stimulation in monocytes. Thus, our results imply that the presence or absence of IFN-γ is critical in determining the effect of acute ethanol treatment on monocyte IL- 12 versus IL-10 induction.

Original languageEnglish
Pages (from-to)211-216
Number of pages6
JournalAlcoholism: Clinical and Experimental Research
Volume22
Issue number1
DOIs
Publication statusPublished - Feb 1998

Keywords

  • Ethanol
  • Interferon-γ
  • Macrophages
  • Th1/Th2 immune response

ASJC Scopus subject areas

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

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