Anti-Rejection Drug Can Prevent Pancreatic Inflammation Triggered by Common Procedure to Remove Gallstones

Exposure to an X-ray dye during a common procedure to treat gallstones causes some patients to develop inflammation of the pancreas, according to researchers at the University of Pittsburgh School of Medicine and Children’s Hospital of Pittsburgh of UPMC. In a study published online in Gastroenterology, the team noted that a single dose of FK506, an anti-rejection drug typically used after organ transplantation, might be able to prevent the complication.

During the endoscopic retrograde cholangiopancreatography (ERCP) procedure, doctors insert a fiber-optic endoscope through the mouth, esophagus, stomach and duodenum to access the bile ducts, where a gallstone might be lodged. The X-ray dye, also known as radiocontrast, is infused through a catheter so doctors can visualize the bile ducts and anything obstructing them, explained senior author and principal investigator Sohail Z. Husain, M.D., associate professor of pediatrics at the Pitt School of Medicine and Children’s Hospital.

“Thousands of ERCP procedures are performed every year, particularly for the removal of gallstones,” Dr. Husain said. “But after the procedure, a fair number of patients develop acute pancreatitis, which is an exquisitely painful, life-threatening inflammation of the pancreas. Our findings provide the first explanation for why this complication occurs, namely through the signals that FK506 can block.”

The research team examined what happened to pancreatic cells in mice after they received infusions of two common radiocontrast agents. They found the agents elevated cellular calcium levels, in turn activating proteins, particularly calcineurin, involved in inflammatory pathways that cause tissue injury. Similar results were observed in experiments with human pancreatic cells. Also, mice that were genetically modified to lack calcineurin failed to develop pancreatitis after radiocontrast exposure.

Mice that were given the anti-rejection drug FK506, which is an inhibitor of calcineurin, before and after infusion of the X-ray dye also were protected from pancreatitis.

“In the future, we will test other radiocontrast agents to see if they, too, affect the same inflammatory pathways,” Dr. Husain said. “This study already sets the stage for a clinical trial to test whether calcineurin inhibitors alone or in combination with other drugs can prevent post-ERCP pancreatitis.”

The team included Shunqian Jin, Ph.D., Abrahim I. Orabi, B.S., Tianming Le, M.D., Tanveer A. Javed, B.S., Swati Sah, B.A., and John F. Eisses, M.D., Ph.D., all of the University of Pittsburgh; Rita Bottino, Ph.D., of Allegheny General Hospital; and Jeffery D. Molkentin, Ph.D., of the University of Cincinnati. The project was funded by National Institutes of Health grants DK083327, DK093491 and DK03002.

Andrea Kunicky, 412-692-6254, andrea.kunicky@chp.edu
Marc Lukasiak, 412-692-7919, marc.lukasiak@chp.edu