ETHANOL-CONSUMPTION AND SUSCEPTIBILITY OF THE PANCREAS TO CERULEIN-INDUCED PANCREATITIS

Despite the fact that alcoholism is one of the major causes of pancrea titis, the pathogenesis of this disorder remains obscure. Factors such as the pattern of ethanol consumption, diet, and genetic predispositi on may be contributing factors. The failure to produce alcoholic pancr eatitis in experimental animals suggests that experimental provision o f ethanol may only increase the predisposition to pancreatitis. To tes t this possibility, we developed an assay system using the in vitro mo del of cerulein-induced pancreatitis. In this system, pancreatic lobul es were first exposed to a supraphysiologic concentration (10(-6) M) o f the cholecystokinin analogue, cerulein, after which homogenates were incubated for up to 6 h. Activation of trypsinogen and chymotrypsinog en was observed only in cerulein-treated preparations. We then investi gated the effects of the duration of ethanol feeding on cerulein-induc ed changes in rat pancreas, The pancreata from rats fed ethanol for 9- 12 months were more susceptible to cerulein-induced activation of chym otrypsinogen compared to the pancreata from pair-fed control animals. This susceptibility also paralleled morphologic changes, such as dilat ation of endoplasmic reticulum, only in the ethanol-fed group. In cont rast, during the early stages (up to 3 months) of ethanol consumption, there was resistance (p < 0.01) to cerulein-induced changes. These re sults suggest that long-term ethanol consumption increases susceptibil ity to pancreatitis and raises the possibility that a similar mechanis m may operate in human alcoholics.