Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury
O'Brien, G.; Shields, C.J.; Winter, D.C.; Dillon, J.P.; Kirwan, W.O.; Redmond, H.P.
Hepatobiliary and Pancreatic Diseases International Hbpd Int 4(1): 126-129
2005
ISSN/ISBN: 1499-3872 PMID: 15730936 Document Number: 590042
The exact mechanism by which cyclooxygenase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreatitis, a disease process characterized by a systemic inflammatory response and ensuing neutrophil-mediated lung injury. Pancreatitis was induced in 24 Sprague-Dawley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group): controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg)at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung injuries were assessed histologically. Lung injury was assessed utilizing wet:dry ratio and myeloperoxidase activity to indicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancreatic tissue. The animals treated with COX-2 inhibitors displayed significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P<0.05) in the COX-2 treated group. Lung wet:dry ratios were significantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (P<0.05). Western blot analysis confirmed attenuated COX-2 protein expression. This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significantly attenuates the severity of both pancreatitis and its associated systemic inflammatory response and end-organ injury.