Lipid Mediator Production in Acute and Chronic Pancreatitis in the Rat

Abstract

Pancreatic production of lipid mediators of inflammation, including eicosanoids and platelet-activating factor (PAF), was examined in two models of pancreatitis in the rat. Chronic pancreatitis was induced by ligation of the pancreatic duct and acute pancreatitis by infusion of sodium taurocholate into the pancreatic duct. In the model of chronic pancreatitis, prostaglandin E 2 (PGE 2), PGD 2, 6-keto PGF 1α, thromboxane B 2 (TXB 2), and PAF increased significantly in the pancreas in a similar fashion, whereas leukotriene B 4 (LTB 4) remained unchanged. BN52021, a PAF antagonist, reduced the accumulation of pancreatic TXB 2, 6-keto PGF 1α, and PGD 2, and did not affect PGE 2. In the model of acute pancreatitis, LTB 4 increased, whereas PGE 2, TXB 2, and 6-keto PGF 1α decreased significantly; PGD 2 changed slightly; and PAF was undetectable. The present results indicate that mild chronic pancreatitis is accompanied by the production and accumulation of a wide spectrum of lipid mediators while LTB 4 was the only lipid mediator detected at biologically active concentrations in the model of severe acute pancreatitis. It is suggested that various mediators are involved in establishing a balance between inflammation and the repair of the inflamed pancreatic tissue observed in mild chronic pancreatitis. While both eicosanoids and PAF are involved in such self-limiting responses to inflammatory challenge, PAF seems to play a central role in instigating the production of the various other mediators detected in the model of chronic pancreatitis. In the model of acute pancreatitis while the deficiency of various lipid mediators may render the pancreatic tissue more susceptible to acute damage, enhanced LTB 4 appears to contribute to the destructive pathology observed. In conclusion, the diversity of the pancreatic inflammatory responses associated with changes in the production of lipid mediators (hypersecretion or hyposecretion) suggests not only the pathophysiological importance of the individual mediators but also rational strategies for therapeutic intervention.