Peripancreatic effects of acute pancreatitis

Abstract

[Background]: Acute pancreatitis is an inflammatory process of the pancreatic gland that in the severe forms triggers the inflammation in remote organs. An additional characteristic of pancreatitis is the necrosis of peripancreatic adipose tissue due to the release of lipolytic enzymes. These areas of adipose tissue release in turn inflammatory mediators. We have evaluated the generation of halogenated free fatty acids by necrotic adipose tissue in a model of acute pancreatitis. [Methods]: Pancreatitis was induced in rats by intraductal administration of 3.5 % sodium taurocholate. We obtained samples of adipose tissue and ascitic fluid 3h, 6h and 18h after induction, and the levels of free fatty acids as well as fatty acid chlorohydrins were evaluated by GC-MS. In additional experiments we administered fatty acid chlorohydrins, generated by chlorination of adipose tissue lipid extracts, on the peritoneum of control animals. Three hours later we obtained peritoneal macrophages and the expression of TNFα on these cells was evaluated by RT-PCR. [Results]: During pancreatitis, necrotic areas of adipose tissue generate and release free fatty acids as well as its chlorohydrins. We identified oleic acid chlorohydrin and mono- and bis- chlorohydrin of linoleic acid in both adipose tissue and ascitic fluid. Administration of chlorinated lipids in the peritoneal cavity results in an increased expression of TNFα by peritoneal macrophages. [Conclusion]: During severe acute pancreatitis, the necrotic areas of the peripancreatic adipose tissue generate chlorinated fatty acids. These halogenated lipids could activate macrophages and plays a role in the progression of the systemic inflammation.