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.