Effect of dexamethasone on peripheral blood leukocyte immune response in bile-pancreatic duct obstruction-induced acute pancreatitis.
Our aim was to analyze the effects of dexamethasone (Dx) (1mg/kg), prophylactically or therapeutically administered, on the inflammatory response triggered by peripheral blood leukocytes during acute pancreatitis (AP) induced in rats by bile-pancreatic duct obstruction (BPDO) and their consequences in the progress of the disease. Flow cytometry was used to analyze the distribution of the major leukocyte populations, the CD45 expression and the activated state of monocytes as reflected by the membrane-bound intercellular adhesion molecule-1 (ICAM-1) and the production of tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattract protein-1 (MCP-1) in response to lipopolysaccaride (LPS). Interleukin-6 (IL-6) plasma levels, pancreatic fluid content and histology of pancreas sections were also evaluated. Dx, given either before or after AP, blunted the monocyte increase induced by BPDO-induced AP, but did not change lymphocyte and neutrophil counts. Membrane-bound ICAM-1 expression did not vary in circulating monocytes during BPDO, either in Dx-treated or non-treated rats. Both Dx treatments inhibited TNF-alpha and MCP-1 production in non-stimulated and LPS-stimulated monocytes, whose response was found to be higher than in controls from early AP. Leukocyte CD45 expression was found to be reduced in rats with AP and shifted to control values in Dx-post-treated rats. Cytokinemia as well as pancreatic edema and leukocyte infiltration found in BPDO rats were reduced by Dx given either before or after AP. We conclude that prophylactic and therapeutic Dx treatments inhibited the inflammatory response triggered by circulating leukocytes in rats with BPDO-induced AP, thus contributing to reducing the severity of the disease.
Ramudo
Laura
L
Department of Physiology and Pharmacology, University of Salamanca, 37007 Salamanca, Spain.
Yubero
Sara
S
Manso
Manuel A
MA
Recio
Javier S
JS
Weruaga
Eduardo
E
De Dios
Isabel
I
D000208:Acute Disease; D000818:Animals; D002779:Cholestasis / Q000097:blood / Q000150:complications* / Q000473:pathology; D016207:Cytokines / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D007249:Inflammation / Q000473:pathology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010195:Pancreatitis / Q000097:blood / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D003907:Dexamethasone; D017493:Leukocyte Common Antigens