Effect of ethanol on inflammatory responses - Implications for pancreatitis

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 TNF alpha or IL10 production, pro-inflammatory gene and nuclear factor-kappa B (NF-kappa B) 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-kappa B activation, inhibition of TNF alpha production and augmentation of the anti-inflammatory cytokine, IL-10. In contrast, acute alcohol treatment augmented NF-kappa B activation and TNF alpha 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-kappa B and TNF alpha 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. Copyright (c) 2007 S. Karger AG, Basel and IAP.