Apoptosis is a teleologically beneficial form of cell death in
acute pancreatitis. Our previous work has demonstrated that induction of pancreatic acinar cell apoptosis by
crambene protects mice against
acute pancreatitis. However, little is known about how the induction of apoptosis reduces the severity of
acute pancreatitis. Because the clearance of apoptotic cells might suppress
inflammation and critically regulate immune responses, we postulate that clearance of apoptotic cells stimulates an anti-inflammatory response, which has a protective action against
acute pancreatitis. To test this hypothesis, induction of apoptosis in
acute pancreatitis in vivo and co-cultures of peritoneal resident macrophages with apoptotic acinar cells in vitro were used as experimental systems, testing expression of phagocytic receptors and levels of inflammatory mediators. Moreover, neutralizing anti-
interleukin (IL)-10
monoclonal antibody (2.5 mg/kg) was used before the induction of apoptosis in
acute pancreatitis, testing whether the protection from apoptosis induction would be removed. Our study showed that clearance of apoptotic acinar cells, which may occur essentially through the CD36-positive macrophage, stimulates the release of anti-inflammatory mediators like
IL-10.
IL-10 plays an important role in
crambene-induced protection in
acute pancreatitis. Thus, induction of pancreatic acinar cell apoptosis by
crambene protects mice against
acute pancreatitis via induction of anti-inflammatory pathways.