THE EFFECTS OF BETAMETHASONE DERIVATIVES ON ENDOTOXIN-INDUCED UVEITISIN RATS

The anti-inflammatory effects of betamethasone and its derivatives (be tamethasone 21-phosphate, betamethasone 21-acetate, betamethasone 17-v alerate, clobetasol 17-propionate and betamethasone dipropionate) on e ndotoxin-induced uveitis (EIU) in rats was investigated. Among the com pounds examined, betamethasone, betamethasone 21-phosphate, betamethas one 21-acetate and clobetasol 17-propionate strongly inhibited cell in filtration into the aqueous humor in the EIU by instillation into the eye in a dose-dependent manner (0.01-1.0%) and by systemic administrat ion (1 mg kg(-1)). On the other hand, betamethasone 17-valerate and be tamethasone dipropionate showed only weak inhibitory effects or enhanc ment of cell infiltration by instillation into the eye (0.01-1.0%) and by systemic administration (1 mg kg(-1)). Combined systemic administr ation of betamethasone dipropionate and betamethasone reduced the inhi bitory effect of betamethasone on cell infiltration and gene expressio n of IL-1 beta. In an in vitro interleukin-8 (IL-8) release assay, bet amethasone showed stronger inhibition of the IL-8 release from rat per itoneal exudate cells (PEG) than betamethasone dipropionate, and simul taneous addition of betamethasone dipropionate with betamethasone redu ced the inhibitory effect of the latter. These results suggest that th e betamethasone derivative betamethasone dipropionate might behave as an anti-glucocorticoid in rats. (C) 1997 Academic Press Limited