Endogenous glucocorticoids inhibit neutrophil recruitment to inflammatory sites in cholestatic rats.

Since glucocorticoids have been shown to inhibit leukocyte accumulation to inflammatory sites (6,9) and endogenous glucocorticoid levels are elevated in our cholestatic rat model, we investigated their role during acute inflammation. Sprague-Dawley rats (150-200 g) were either bile duct resected (BDR) or sham resected (sham). Five days later, a 2% carrageenan solution in saline was injected subcutaneously into preformed air pouches on their backs. Animals were killed 5 h later, and inflammatory response was quantitated by measuring the exudate volume, cell count, and myeloperoxidase (mainly in neutrophils) activity. We also pretreated BDR/sham rats with RU-486 (2 mg/kg ip), a glucocorticoid receptor antagonist, 1 h before carrageenan injection. BDR rats exhibited an impaired inflammatory response reflected by 20, 52, and 42% decreases in exudate volume, cell count, and myeloperoxidase activity, respectively (all P < 0.05). RU-486 treatment significantly increased the inflammatory response in BDR rats (to sham levels), but not in sham rats. These results suggest that endogenous glucocorticoid suppresses the inflammatory response in BDR rats.