The effects of betamethasone derivatives on endotoxin-induced uveitis in rats.
The anti-inflammatory effects of betamethasone and its derivatives (betamethasone 21-phosphate, betamethasone 21-acetate, betamethasone 17-valerate, clobetasol 17-propionate and betamethasone dipropionate) on endotoxin-induced uveitis (EIU) in rats was investigated. Among the compounds examined, betamethasone, betamethasone 21-phosphate, betamethasone 21-acetate and clobetasol 17-propionate strongly inhibited cell infiltration into the aqueous humor in the EIU by instillation into the eye in a dose-dependent manner (0.01-1.0%) and by systemic administration (1 mg kg-1). On the other hand, betamethasone 17-valerate and betamethasone dipropionate showed only weak inhibitory effects or enhancement of cell infiltration by instillation into the eye (0.01-1.0%) and by systemic administration (1 mg kg-1). Combined systemic administration of betamethasone dipropionate and betamethasone reduced the inhibitory effect of betamethasone on cell infiltration and gene expression of IL-1 beta. In an in vitro interleukin-8 (IL-8) release assay, betamethasone showed stronger inhibition of the IL-8 release from rat peritoneal exudate cells (PEC) than betamethasone dipropionate, and simultaneous addition of betamethasone dipropionate with betamethasone reduced the inhibitory effect of the latter. These results suggest that the betamethasone derivative betamethasone dipropionate might behave as an anti-glucocorticoid in rats.
Tsuji
F
F
Discovery Research Division, Santen Pharmaceutical Co., Ltd., Osaka, Japan.
Sawa
K
K
Kato
M
M
Mibu
H
H
Shirasawa
E
E
D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000166:cytology / Q000187:drug effects; D001623:Betamethasone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004336:Drug Antagonism; D004338:Drug Combinations; D004731:Endotoxins / Q000009:adverse effects; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy*
D000893:Anti-Inflammatory Agents; D004338:Drug Combinations; D004731:Endotoxins; D007375:Interleukin-1; D016209:Interleukin-8; D001623:Betamethasone