Moderate alcohol intake in humans attenuates monocyte inflammatory responses: Inhibition of nuclear regulatory factor kappa B and induction of interleukin 10

Pranoti Mandrekar, Donna Catalano, Bernadette White, Gyongyi Szabo

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Background: In contrast to the deleterious effects of chronic excessive alcohol consumption on the liver and cardiovascular system, modest alcohol intake, such as 1 to 2 drinks per day, has benefits on cardiovascular mortality. Little is known about the length of time or the amounts of alcohol consumed that may cause alterations in inflammatory cells such as monocytes that are crucial to atherosclerotic vascular disease. Here, we determine in vivo effects of acute alcohol consumption on inflammatory cytokine production and nuclear regulatory factor κB (NF-κB) binding in human monocytes. Methods: Human blood monocytes were isolated by plastic adherence before and after acute alcohol consumption (2 ml vodka/kg body weight). Lipopolysaccharide (LPS)- and superantigen-induced tumor necrosis factor α (TNF α), interleukin (IL)-1β, and IL-10 production were then determined in monocytes by ELISA. Nuclear regulatory factor-κB activity of monocytes before and after alcohol consumption was estimated by electromobility shift assay and promoter-driven reporter activity. IκBα was determined by Western blotting in the cytoplasmic extracts. Results: Eighteen hours after moderate alcohol consumption, we found a significant reduction in monocyte production of inflammatory mediators, TNF-α and IL-1β, in response to LPS or staphylococcal enterotoxin B stimulation. Acute alcohol consumption inhibited LPS-induced DNA binding of the p65/p50 NF-κB in monocytes that regulates the expression of both the TNF-α and the IL-1β genes. Consistent with this, acute alcohol treatment (25 mM) significantly reduced LPS-induced activation of an NF-κB-driven reporter gene suggesting inhibition of this proinflammatory signaling pathway. Further, LPS-induced IκBα degradation was not affected by acute alcohol consumption indicating an IκBα-independent mechanism, as observed earlier in the in vitro acute alcohol studies. In contrast, monocyte production of the anti-inflammatory cytokine, IL-10, was augmented by acute alcohol intake. Conclusions: Our findings suggest that acute alcohol consumption has dual anti-inflammatory effects that involve augmentation of IL-10 and attenuation of monocyte inflammatory responses involving inhibition of NF-κB. These mechanisms may contribute to the beneficial effects of moderate alcohol use on atherosclerosis.

Original languageEnglish
Pages (from-to)135-139
Number of pages5
JournalAlcoholism: Clinical and Experimental Research
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 1 2006

Keywords

  • Atherosclerosis
  • IL-1β
  • Macrophage
  • NF-κB
  • TNF-α

ASJC Scopus subject areas

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

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