16 beta-Methyl-17 alpha,21-diesterified glucocorticoids as partial agonists of glucocorticoid in rat endotoxin-induced inflammation.
OBJECTIVE
We investigated the anti-inflammatory effects of 16 beta-methyl-17 alpha,21-diesterified glucocorticoids which are well known as potent topical glucocorticoids in man on endotoxin-induced uveitis (EIU) in rats.


METHODS
Female Lewis rats were used.


METHODS
Glucocorticoids were instilled (0.01%-1.0%) or subcutaneously injected (0.1-10 mg/kg) to rats.


METHODS
To elicit EIU, LPS (500 micrograms/kg) was injected into the footpad of rats. Twelve hours after LPS injection, cell number in aqueous humor was counted by flow cytometry. Endotoxin-induced in vivo tumor necrosis factor-alpha (TNF-alpha) production was also examined.


RESULTS
16 beta-methyl-17 alpha,21-diesterified glucocorticoids showed no effects or some enhancement of cell infiltration 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, betamethasone phosphate strongly inhibited the cell infiltration and TNF-alpha production. Combined systemic injection of 16 beta-methyl-17 alpha,21-diesterified glucocorticoids and betamethasone phosphate reduced the inhibitory effects of the latter.


CONCLUSIONS
These results suggest that 16 beta-methyl-17 alpha,21-diesterified glucocorticoids might act as partial agonists of glucocorticoid in rats.
Tsuji
F
F
Discovery Research Division, Santen Pharmaceutical Co. Ltd., Osaka, Japan.
Sawa
K
K
Mibu
H
H
Shirasawa
E
E
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001623:Betamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014605:Uveitis / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D001623:Betamethasone