Effect of ethanol on inflammatory responses. Implications for pancreatitis
Department of Medicine, Division of Gastroenterology; Department of Medicine, Rheumatology Division
Medical Subject Headings
Alcohol Drinking; Cells, Cultured; Ethanol; Female; Humans; Interleukin-10; Male; Monocytes; NF-kappa B; Pancreatitis, Alcoholic; Toll-Like Receptor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha
Gastroenterology | Immunology and Infectious Disease
BACKGROUND/AIMS: Alcohol use alters inflammatory cell responses. While alcohol has direct effects on pancreatic acinar cells, activation of inflammatory cells is a major component of the pathology of alcoholic pancreatitis.
METHODS: The effects of acute or chronic alcohol exposure were evaluated in human monocytes on the production of TNFalpha or IL-10 production, pro-inflammatory gene and nuclear factor-kappaB (NF-kappaB) activation.
RESULTS: Moderate, acute alcohol consumption or equivalent doses of alcohol in vitro had anti-inflammatory effects on monocyte activation via inhibition of pro-inflammatory genes and NF-kappaB activation, inhibition of TNFalpha production and augmentation of the anti-inflammatory cytokine, IL-10. In contrast, acute alcohol treatment augmented NF-kappaB activation and TNFalpha production and inhibited IL-10 levels in the presence of complex stimulation with combined TLR2 and TLR4 ligands. Prolonged alcohol exposure also resulted in an increase in NF-kappaB and TNFalpha production in response to TLR4 stimulation with LPS.
CONCLUSION: These results suggest that alcohol can either attenuate or promote inflammatory responses that are critical in pancreatitis. Our results support the hypothesis that both acute alcohol intake in the presence of complex stimuli (such as necrotic cells) and chronic alcohol exposure result in hyper-responsiveness of monocytes to inflammatory signals and may contribute to increased inflammation in pancreatitis.
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Citation: Pancreatology. 2007;7(2-3):115-23. Epub 2007 Jun 21. Link to article on publisher's site