Targeted Inhibition of Pancreatic Acinar Cell Calcineurin Is a Novel Strategy to Prevent Post-ERCP Pancreatitis

BACKGROUND & AIMS: There is a pressing need to develop effective preventative therapies for post–endoscopic retrograde cholangiopancreatography pancreatitis (PEP). We showed that early PEP events are induced through the calcium-activated phosphatase calcineurin and that global calcineurin deletion abolishes PEP in mice. A crucial question is whether acinar cell calcineurin controls the initiation of PEP in vivo. METHODS: We used a mouse model of PEP and examined the effects of in vivo acinar cell-specific calcineurin deletion by either generating a conditional knockout line or infusing a novel adeno-associated virus–pancreatic elastase improved Cre (I–iCre) into the pancreatic duct of a calcineurin floxed line. RESULTS: We found that PEP is dependent on acinar cell calcineurin in vivo, and this led us to determine that calcineurin inhibitors, infused within the radiocontrast, largely can prevent PEP. CONCLUSIONS: These results provide the impetus for launching clinical trials to test the efficacy of intraductal calcineurin inhibitors to prevent PEP.