title: 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 E2 (PGE2), PGD2, 6-keto PGF1 alpha, thromboxane B2 (TXB2), and PAF increased significantly in the pancreas in a similar fashion, whereas leukotriene B4 (LTB4) remained unchanged. BN52021, a PAF antagonist, reduced the accumulation of pancreatic TXB2, 6-keto PGF1 alpha, and PGD2, and did not affect PGE2. In the model of acute pancreatitis, LTB4 increased, whereas PGE2, TXB2, and 6-keto PGF1 alpha decreased significantly; PGD2 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 LTB4 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 LTB4 appears to contribute to the destructive pathology observed.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284.
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: B A
authors.initials: BA
authors.lastname: Levine
authors.forename: M S
authors.initials: MS
authors.lastname: Olson
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D015232:Dinoprostone / Q000378:metabolism; D004224:Diterpenes; D015777:Eicosanoids / Q000378:metabolism*; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology; D007975:Leukotriene B4 / Q000378:metabolism; D008026:Ligation; D008297:Male; D009637:Masoprocol / Q000494:pharmacology; D010183:Pancreatic Ducts; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000378:metabolism*; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000008:administration & dosage; D013929:Thromboxane B2 / Q000378:metabolism
chemical_list: D004224:Diterpenes; D015777:Eicosanoids; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D007975:Leukotriene B4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D013656:Taurocholic Acid; D009637:Masoprocol; C045856:ginkgolide B; D015232:Dinoprostone; D015230:Prostaglandin D2