Recent Advances in Immune System Activation at Onset of Acute Pancreatitis

Abstract

For many years, the intracellular activation of trypsin has been considered the most important early mechanism initiating acute pancreatitis and the destruction of the pancreatic parenchyma quickly induces an inflammatory reaction at the site of injury. It has recently been demonstrated that a separation exists between intra-acinar trypsin activation and the initiation of other pathways of pancreatitis such as the cytokine cascade and elevated Ras (Rat sarcoma protein family) signaling. Thus, a new paradigm has now been introduced for acute pancreatitis; trypsinogen activation is not the only mechanism responsible for initiating acute illness since other pathways have been found to independently and simultaneously participate in the process. From a clinical point of view, these findings explain why the inhibition of proteases alone is not sufficient for preventing distant organ involvement during severe acute pancreatitis and why the manipulation of the inflammatory response gave the same disappointing results.