NF-κB activation in pancreas induces pancreatic and systemic inflammatory response

Background & Aims: The role of nuclear factor κB (NF-κB) activation in acute pancreatitis is uncertain. The transcription factor NF-κB is activated early in acute pancreatitis, and NF-κB is widely considered a key element in inflammatory responses based on its ability to regulate the expression of inflammatory mediators in vitro. However, its role in vivo in specific diseases remains unclear, and the current data on the role of NF-κB in acute pancreatitis is primarily correlative. Methods: In this study, NF-κB was directly activated within the pancreas using adenoviral-mediated transfer of an active subunit, ReIA/p65 (Adp65), delivered by intraductal injection. Results: Administration of Adp65 led to the infection of a population of acinar cells within the pancreas, the activation of NF-κB, the expression of NF-κB target genes, and an inflammatory response. Administration of Adp65 increased the infiltration of neutrophils to the pancreas and lung and caused widespread damage to pancreatic acinar cells. In contrast, at the same titer, control adenovirus (AdGFP) had no effect on these parameters. The level of NF-κB activation and the severity of inflammation were reduced when an adenovirus bearing the inhibitory subunit IκB-α was coadministered with Adp65. Conclusions: Thus, activation of NF-κB within the pancreas was sufficient for the initiation of an inflammatory response in this model. These results help define the specific role of NF-κB activation in acute pancreatitis.