Induction of apoptosis reduces the severity of caerulein-induced pancreatitis in mice.

The recent observation that the severity of pancreatitis is inversely related to the extent of apoptosis in five experimental models of the disease has suggested the possibility that apoptosis might protect against pancreatic injury in pancreatitis. This hypothesis was tested by inducing pancreatitis in mice during a phase of extensive apoptosis. Mice were fed a raw soya diet for five weeks to stimulate pancreatic growth and then switched to a regular chow diet for 27 hrs to permit involution of the hypertrophied gland. That involution is characterized by extensive apoptosis of acinar cells. Pancreatitis was induced, in either control mice or mice undergoing pancreatic involution, by repeated intraperitoneal administration of a supramaximally stimulating dose of caerulein (50 microg/kg given each hr for 12 hrs). The magnitude of hyperamylasemia, degree of inflammation, and extent of necrosis were reduced in the mice receiving caerulein during pancreatic involution. We conclude that induction of apoptosis may protect against acinar cell injury and reduce the severity of pancreatitis.