CD40 ligand-deficient mice are protected against cerulein-induced acute pancreatitis and pancreatitis-associated lung injury

Background & Aims: The interactions between inflammatory cells and their me diators play important roles in many inflammatory processes, but their impo rtance during acute experimental pancreatitis and pancreatitis-associated l ung injury is unclear. To address the role of the interaction between CD40 and its ligand CD40L, molecules that mediate major immunoregulatory functio ns, pancreatitis was induced by administering supramaximal doses of cerulei n in mice that do not express CD40L. Methods: The severity of pancreatitis was measured by serum amylase activity, pancreatic edema, acinar cell necro sis, and pancreas myeloperoxidase activity tan indicator of neutrophil infi ltration). Lung injury was quantitated by evaluating lung microvascular per meability and lung myeloperoxidase activity. Results: In pancreatic tissue from control mice and cerulein-treated mice, the expression of both CD40 an d CD40L was detected. Immunohistochemical analysis performed in isolated ac ini from wild-type pancreata showed that both CD40 and CD40L were expressed on the acinar cell surface. interestingly, pancreatitis and pancreatitis-a ssociated lung injury were markedly decreased in mice deficient in CD40L co mpared with wild-types. Conclusions: These observations indicate that CD40L plays an important proinflammatory role in pancreatitis and pancreatitis-a ssociated lung injury.