16-BETA-METHYL-17-ALPHA,21-DIESTERIFIED GLUCOCORTICOIDS AS PARTIAL AGONISTS OF GLUCOCORTICOID IN RAT ENDOTOXIN-INDUCED INFLAMMATION

Objective and Design: We investigated the antiinflammatory effects of 16 beta-methyl-17 alpha,21-diesterified glucocorticoids which are well known as potent topical glucocorticoids in man on endotoxin-induced u veitis (EIU) in rats. Material: Female Lewis rats were used. Treatment : Glucocorticoids were instilled (0.01% - 1.0%) or subcutaneously inje cted (0.1 - 10 mg/kg) to rats, Methods: To elicit EIU, LPS (500 mu g/k g) was injected into the footpad of rats. Twelve hours after LPS injec tion, cell number in aqueous humor was counted by flow cytometry. Endo toxin-induced in vivo tumor necrosis factor-alpha (TNF-alpha) producti on was also examined. Results: 16 beta-methyl-17 alpha,21-diesterified glucocorticoids showed no effects or some enhancement of cell infiltr ation into the aqueous humor in EIU by topical instillation. Systemic injection of these glucocorticoids showed only weak inhibition of cell infiltration and TNF-alpha production. On the other hand, betamethaso ne phosphate strongly inhibited the cell infiltration and TNF-alpha pr oduction. Combined systemic injection of 16 beta-methyl-17 alpha,21 -d iesterified glucocorticoids and betamethasone phosphate reduced the in hibitory effects of the latter. Conclusions: These results suggest tha t 16 beta-methyl-17 alpha,21-diesterified glucocorticoids might act as partial agonists of glucocorticoid in rats.