Fat necrosis generates proinflammatory halogenated lipids during acute pancreatitis.

OBJECTIVE: To evaluate the generation of halogenated fatty acids in the areas of fat necrosis during acute pancreatitis and to evaluate the effects of these molecules on the ensuing inflammatory process.
BACKGROUND: Lipid mediators derived from adipose tissue have been implicated in the progression of acute pancreatitis, although their precise role remains unknown.
METHODS: Acute pancreatitis was induced in rats by intraductal infusion of 3.5% sodium taurocholate. Fatty acid chlorohydrins (FA-Cl) were measured in adipose tissue, ascitic fluid, and plasma by mass spectrometry. Chlorohydrins were also instilled in the rats' peritoneal cavity, and their effects on peritoneal macrophages activation and in systemic inflammation were evaluated. Finally, they have also been measured in plasma from human patients with acute pancreatitis.
RESULTS: Induced acute pancreatitis results in a substantial release not only of free fatty acids but also of the chlorohydrins of both oleic and linoleic acids from adipose tissue. In plasma, only the chlorohydrin of oleic acid was detected. Administration of 250-μM lipid chlorohydrins, which is the concentration found in ascitic fluid, induces the expression of TNFα and interleukin-1β in peritoneal macrophages and increases the systemic inflammatory response in pancreatitis. Finally, increased concentrations of oleic acid chlorohydrin have been found in plasma of human patients with pancreatitis.
CONCLUSIONS: During acute pancreatitis, adipose tissue release FA-Cl, which exacerbate the systemic inflammatory response.