ENDOGENOUS GLUCOCORTICOIDS INHIBIT NEUTROPHIL RECRUITMENT TO INFLAMMATORY SITES IN CHOLESTATIC RATS

Since glucocorticoids have been shown to inhibit leukocyte accumulatio n to inflammatory sites (6, 9) and endogenous glucocorticoid levels ar e elevated in our cholestatic rat model, we investigated their role du ring acute inflammation. Sprague-Dawley rats (150-200 g) were either b ile duct resected (BDR) or sham resected (sham). Five days later, a 2% carrageenan solution in saline was injected subcutaneously into prefo rmed air pouches on their backs. Animals were killed 5 h later, and in flammatory response was quantitated by measuring the exudate volume, c ell count, and myeloperoxidase (mainly in neutrophils) activity. We al so pretreated BDR/sham rats with RU-486 (2 mg/kg ip), a glucocorticoid ,receptor antagonist, Ih before carrageenan injection. BDR rats exhibi ted an impaired inflammatory response reflected by 20, 52, and 42% dec reases in exudate volume, cell count, and myeloperoxidase activity, re spectively (all P < 0.05). RU-486 treatment significantly increased th e 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.