Theories, mechanisms, and models of alcoholic chronic pancreatitis.

Alcoholic chronic pancreatitis is a severe, disabling, chronic inflammatory condition of the pancreas that is seen in fewer than 5% of alcoholics. The severity and unpredictability of this condition has lead to several theories on the mechanism causing chronic pancreatitis based on careful clinical observation. Hypothetical mechanisms were applied to various animal models. Finally, following multiple lines of evidence, there is a convergence of thought and development of some new models that are quite instructive. Taken together, chronic alcohol consumption by rats results in multiple effects on the pancreas that increase the risk of acute pancreatitis, including ongoing acinar cell injury that lowers the threshold for hyperstimulation-induced acute pancreatitis, neurohormonal injury, and adaptation that results in acinar cell hyperstimulation, increased susceptibility to viral mediated acute pancreatitis, and possibly other factors. After acute pancreatitis initiates the inflammatory process, the chronic inflammation and fibrosis of alcoholic chronic pancreatitis are driven by diet, the acinar cell stress response to continued alcohol that may be potentiated by toxic alcohol metabolites, hypoxia, hyperstimulation, and partial duct obstruction; plus the effects of proinflammatory immunocytes and cytokines; and by stellate cell-mediated fibrosis driven by anti-inflammatory cytokines, alcohol, and alcohol metabolites. The factors determining which alcoholic will develop alcoholic chronic pancreatitis likely involve genetic factors, dietary factors, and susceptibility to pancreatic injury through several mechanisms ranging from trauma to gallstones to viruses.