Dendritic Cells Are Necessary For Pancreas Viability In Acute Pancreatitis

Introduction: Acute pancreatitis is characterized by an influx of inflammatory cell into the pancreas including dendritic cells (DC). However, the role of DC in pancreatitis is unknown. Since DC are central to initiating both robust inflammation and immune tolerance, we postulated that DC would have a primary role in regulating pancreatic insult. Methods: Cerulein and L-Arginine models of acute pancreatitis were employed in both C57BL/6 and CD11c-DTR mice in which DC depletion is accomplished by administration of diphtheria toxin. Tissue necrosis was determined by light microscopy using a computerized grid. Pancreatic infiltrates were assessed by flow cytometry. Cytokine levels were measured in a cytometric bead array. Survival was determined by the Kaplan-Meier method. Results: DC depleted mice challenged with cerulein developed necrosis of 96% pancreatic acini. Conversely, only 1% of pancreatic acini of mock depleted mice developed tissue necrosis after cerulein challenge (P<0.0001). Furthermore, all mock depleted mice survived to 14 days, while 100% of DC depleted mice died within 5 days of cerulein challenge (P<0.0001). Similar effects of DC depletion were seen in an L-arginine model of acute pancreatitis. DC depletion was associated with elevated pancreatic expression of IL-6 and EGR-1 and serum TNF-α. DC depleted pancreata had a 10-fold increase in neutrophils and inflammatory monocytes after pancreatitis induction; however, tissue necrosis was independent of these cells. Similarly, IL-6, TNF-α, and NF-κB blockade did not mitigate the necrotic effects of DC depletion. Conclusions: These data demonstrate that DC are required for pancreas viability in acute pancreatitis.