Inhibition of cyclooxygenase-2 ameliorates the severity of pancreatitis and associated lung injury.
Cyclooxygenase-2 (COX-2), a widely distributed enzyme, plays an important role in inflammation. We have studied the role of COX-2 in acute pancreatitis and pancreatitis-associated lung injury using both the pharmacological inhibition of COX-2 and genetic deletion of COX-2. Pancreatitis was induced in mice by 12 hourly injections of cerulein. The severity of pancreatitis was assessed by measuring serum amylase, pancreatic trypsin activity, intrapancreatic sequestration of neutrophils, and acinar cell necrosis. The severity of lung injury was evaluated by measuring lactate dehydrogenase levels in the bronchoalveolar lavage fluid and by quantitating neutrophil sequestration in the lung. In both the pharmacologically inhibited and genetically altered mice, the severity of pancreatitis and pancreatitis-associated lung injury was reduced compared with the noninhibited strains of COX-2-sufficient mice. This reduction in injury indicates that COX-2 plays an important proinflammatory role in pancreatitis and its associated lung injury. Our findings support the concept that COX-2 inhibitors may play a beneficial role in the prevention of acute pancreatitis or in the reduction of its severity.
Song
Albert M
AM
Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Bhagat
Lakshmi
L
Singh
Vijay P
VP
Van Acker
Gijs G D
GG
Steer
Michael L
ML
Saluja
Ashok K
AK
D000818:Animals; D000068579:Celecoxib; D002108:Ceruletide; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008171:Lung Diseases / Q000150:complications* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009578:Nitrobenzenes / Q000494:pharmacology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011720:Pyrazoles; D012333:RNA, Messenger / Q000378:metabolism; D012720:Severity of Illness Index; D013449:Sulfonamides / Q000494:pharmacology; D014362:Trypsinogen / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D007527:Isoenzymes; D016328:NF-kappa B; D009578:Nitrobenzenes; D011720:Pyrazoles; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D002108:Ceruletide; D014362:Trypsinogen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib