Abstract

A novel strategy to prevent pancreatic inflammation due to an endoscopic procedure called an ERCP. There is a pressing need to develop effective preventative therapies for post-ERCP pancreatitis (PEP). We recently published that early PEP events are induced through the activation of a calcium-activated phosphatase called calcineurin and that global deletion of calcineurin abolishes PEP in a mouse model. A crucial question is whether calcineurin within the pancreas itself controls the initiation of PEP. We now show, using two complementary genetic approaches, that PEP is dependent on calcineurin produced by the main cells of the pancreas called acinar cells and that calcineurin inhibitor medications, infused within the radiocontrast given during ERCP, can largely prevent PEP. These results provide impetus for launching clinical trials to test the efficacy of this novel delivery of calcineurin inhibitors to prevent PEP.