title: Mechanisms of alcoholic pancreatitis.
abstract: Alcoholic pancreatitis is a major complication of alcohol abuse. The risk of developing pancreatitis increases with increasing doses of alcohol, suggesting that alcohol exerts dose-related toxic effects on the pancreas. However, it is also clear that only a minority of alcoholics develop the disease, indicating that an additional trigger may be required to initiate clinically evident pancreatic injury. It is now well established that alcohol is metabolized by the pancreas via both oxidative and non-oxidative metabolites. Alcohol and its metabolites produce changes in the acinar cells, which may promote premature intracellular digestive enzyme activation thereby predisposing the gland to autodigestive injury. Pancreatic stellate cells (PSCs) are activated directly by alcohol and its metabolites and also by cytokines and growth factors released during alcohol-induced pancreatic necroinflammation. Activated PSCs are the key cells responsible for producing the fibrosis of alcoholic chronic pancreatitis. Efforts to identify clinically relevant factors that may explain the susceptibility of some alcoholics to pancreatitis have been underway for several years. An unequivocal, functionally characterized, association is yet to be identified in clinical studies, although in the experimental setting, endotoxin has been shown to trigger overt pancreatic injury and to promote disease progression in alcohol-fed animals. Thus, while the molecular effects of alcohol on the pancreas have been increasingly clarified in recent years, identification of predisposing or triggering factors remains a challenge.
authors.affiliation: Pancreatic Research Group, South Western Sydney Clinical School, Liverpool Hospital and School of Medical Sciences, University of New South Wales, Sydney, Australia. m.apte@unsw.edu.au
authors.forename: Minoti V
authors.initials: MV
authors.lastname: Apte
authors.forename: Romano C
authors.initials: RC
authors.lastname: Pirola
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Wilson
mesh_terms: D000818:Animals; D001711:Biotransformation; D004198:Disease Susceptibility; D000431:Ethanol / Q000009:adverse effects / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D019512:Pancreatitis, Alcoholic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D000431:Ethanol