Effect of ethanol on inflammatory responses. Implications for pancreatitis.
OBJECTIVE
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.


CONCLUSIONS
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.
Szabo
Gyongyi
G
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA. gyongyi.szabo@umassmed.edu
Mandrekar
Pranoti
P
Oak
Shilpa
S
Mayerle
Julia
J
D000428:Alcohol Drinking / Q000097:blood / Q000276:immunology*; D002478:Cells, Cultured; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000096:biosynthesis / Q000097:blood; D019512:Pancreatitis, Alcoholic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051195:Toll-Like Receptor 2 / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood
D016328:NF-kappa B; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000431:Ethanol