Search resultsModerate alcohol intake in humans attenuates monocyte inflammatory responses: Inhibition of nuclear regulatory factor kappa B and induction of interleukin 10
Title
Moderate alcohol intake in humans attenuates monocyte inflammatory responses: Inhibition of nuclear regulatory factor kappa B and induction of interleukin 10
Publication type
Journal Article
Year of Publication
2006
Authors
Journal
Alcoholism: Clinical and Experimental Research
Volume
30
Issue
1
Pagination
135 - 139
Date published
2006
ISBN
01456008 (ISSN)
Keywords
Adult, alcohol consumption, Alcohol Drinking, antiinflammatory activity, article, atherosclerosis, attenuation, body weight, cell adhesion, controlled study, cytokine release, cytoplasm, DNA binding, Dose-Response Relationship, Drug, enzyme linked immunosorbent assay, Ethanol, Female, gene expression, human, Humans, IL-1β, immunoglobulin enhancer binding protein, in vitro study, inflammation, interleukin 1, interleukin 10, Interleukin-1, Interleukin-10, lipopolysaccharide, Lipopolysaccharides, macrophage, male, mediator release, Middle Aged, monocyte, Monocytes, NF-kappa B, NF-κB, normal human, p65 protein, priority journal, protein, protein p50, reporter gene, signal transduction, Staphylococcus, Staphylococcus enterotoxin B, TNF-α, tumor necrosis factor alpha, Tumor Necrosis Factor-alpha, unclassified drug, vodka, Western blotting
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. Copyright