Dexamethasone down-regulates the inflammatory mediators but fails to reduce the tissue injury in the lung of acute pancreatitis rat models.
Pulmonary complications are frequent in the course of acute pancreatitis. We investigate the effects of dexamethasone on lung injury in mild and severe AP. Mild and severe acute pancreatitis was induced in rats by bile-pancreatic duct obstruction and infusion of 3.5% sodium taurocholate into the bile-pancreatic duct, respectively. Dexamethasone (1 mg/kg) was given by intramuscular injection 1 h after acute pancreatitis. Plasma amylase activity was measured to evaluate the pancreas damage. Lungs were harvested for analysing mRNA expression of monocyte chemoattractant protein-1 (MCP-1), cytokine-induced neutrophil chemoattractant (CINC), P-selectin and intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) activity (as index of neutrophil infiltration) and histological examination. Dexamethasone reduced the hyperamylasemia and hindered the pulmonary upregulation of MCP-1, CINC, P-selectin and ICAM-1, in both mild and severe acute pancreatitis. Despite this, dexamethasone treatment failed to reduce MPO activity and histological alterations developed in lungs during acute pancreatitis, either in bile-pancreatic duct obstruction or sodium taurocholate model. We conclude that pulmonary local factors different from inflammatory mediators contribute to leukocyte recruitment, so that although dexamethasone down-regulated the lung expression of chemokines and adhesion molecules during acute pancreatitis it was not able to prevent leukocyte infiltration, which could be responsible for maintaining the lung injury in either mild or severe acute pancreatitis.
Department of Physiology and Pharmacology, IBSAL (Instituto Biosanitario Salamanca), University of Salamanca, 37007 Salamanca, Spain.
Sara
S
Yubero
Manuel A
MA
Manso
Laura
L
Ramudo
Secundino
S
Vicente
Isabel
I
De Dios
D000208:Acute Disease; D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology*; D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002448:Cell Adhesion; D018925:Chemokines / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D015536:Down-Regulation; D008168:Lung / Q000276:immunology; D008297:Male; D010195:Pancreatitis / Q000150:complications; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D000893:Anti-Inflammatory Agents; D018925:Chemokines; D012333:RNA, Messenger; D003907:Dexamethasone; D000681:Amylases