|
|
Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury |
Gavin O’Brien, Conor J Shields, Desmond C Winter, John P Dillon, William O Kirwan and H. Paul Redmond |
Cork, Ireland
Author Affiliations: Department Of Academic Surgery, Cork University Hospital and National University of Ireland, Cork, Ireland (O’Brien G, Shields CJ, Winter DC, Dillon JP, Kirwan WO and Redmond HP)
Corresponding Author: H. Paul Redmond, BSc, MCh, Department of Academic Surgery, Cork University Hospital, Wilton, Cork, Ireland (Tel: 353-21-4922370; Fax: 353-21-4922811; Email: redmondhp@shb.ie) |
|
|
Abstract BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
|
|
|
|
|
|
|
|