PROTECTIVE EFFECTS OF PROSTAGLANDIN E(1) ON ACUTE LUNG INJURY OF CERULEIN-INDUCED ACUTE-PANCREATITIS IN RATS

Infusion of a supramaximally stimulating dose of the pancreatic secret agogue caerulein (10 mu g . kg(-1). h(-1)) for 4 h induces interstitia l edematous acute pancreatitis in rats. This model of acute pancreatit is is associated with evidence of acute lung injury, including sequest ered neutrophils within the pulmonary microvasculature, increased micr ovascular permeability, and interstitial pulmonary edema. Infusion of prostaglandin E(1) (PGE(1); 50 ng . kg(-1). min(-1)) along with caerul ein does not alter the severity of secretagogue-induced pancreatitis, but it does reduce the severity of pancreatitis-associated acute lung injury. The rise in lung weight, lung water content, and pulmonary mic rovascular permeability and the sequestration of neutrophils within th e pulmonary microvasculature that accompany secretagogue-induced pancr eatitis are all reduced by infusion of PGE(1). Infusion of PGE(1) does not interfere with polymorphonuclear neutrophil sequestration in the pancreas or reduce the enhanced expression of CD11b/c receptors on cir culating neutrophils. Our observations indicate that PGE(1) reduces th e severity of pancreatitis-associated acute lung injury by preventing neutrophil sequestration within the lung. We speculate that PGE(1) int erferes with neutrophil sequestration by dilating pulmonary vasculatur e, increasing pulmonary flow rate, and reducing neutrophil-endothelial cell interaction and attachment.