Sentinel Acute Pancreatitis Event Increases Severity of Subsequent Episodes in Mice

Abstract

Pancreatitis is the inflammatory disorder of the pancreas, which often forms a disease continuum starting with an acute pancreatitis (AP) attack followed by recurrent acute pancreatitis (RAP) episodes and eventual progression to chronic pancreatitis (CP). 1 Yadav D. et al. Gastroenterology. 2013; 144: 1252-1261 Google Scholar Progression to RAP and ultimately to CP is associated with environmental and/or genetic risk factors. The Sentinel Acute Pancreatitis Event (SAPE) hypothesis has been proposed to explain how a single episode of AP could lead to CP. 2 Whitcomb D.C. Gut. 1999; 45: 317-322 Google Scholar , 3 Schneider A. et al. Best Pract Res Clin Gastroenterol. 2002; 16: 347-363 Google Scholar , 4 Whitcomb D.C. Gastroenterology. 2013; 144: 1292-1302 Google Scholar , 5 Whitcomb D.C. et al. Pancreatology. 2016; 16: 218-224 Google Scholar This model posits that in the setting of susceptibility factors, an initial “sentinel” episode of AP sensitizes the pancreas to recurring/continual inflammation and fibrosis through activation of the immune system. The initial AP attack is called the sentinel event because it signals the beginning of CP and alerts the physician to initiate therapy for the prevention of progression. To test the SAPE concept experimentally, we set out to investigate whether an episode of experimental AP in mice would change the severity of later attacks. We also examined whether sensitization of the pancreas by the sentinel AP event is mediated by retention of inflammatory cells or by altered protease activation.