Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat.
FK506 is a macrolide antibiotic and a potent immunosuppressant. To investigate the effect of topical FK506 on acute ocular inflammation, we evaluated its action on the development of endotoxin-induced uveitis (EIU). At two different concentrations of 0.05% and 0.3%, topical FK506 was applied to Lewis rats with EIU. In aqueous, the mean number of inflammatory cells per microliter +/- SEM was 2,389 +/- 1,277, 1,571 +/- 1,562, 898 +/- 882, and 69 +/- 152 for rats treated with vehicle alone, 0.05%, 0.3% FK506, and 1% prednisolone acetate. The median of histological grades was 2, 1.5, 0.8, and 0.5 for animals treated with these 4 different regimens respectively. Analysis of aqueous protein showed a small reduction in FK506-treated animals. Mean blood levels of FK506 were low in rats treated with topical FK506 (0.05%, 0.84 ng/ml; 0.3%, 2.0 ng/ml) suggesting that its therapeutic effect was not secondary to the systemic absorption of the drug. Although FK506 is not as effective as prednisolone, 0.3% FK506 produced significant decreases in the mean aqueous inflammatory cell number and histological inflammatory score as compared to control vehicle alone. We conclude that topical FK506 can suppress EIU in a dose-dependent fashion and may be an alternative medication for patients with anterior uveitis and contra-indication to topical steroid.
Hikita
N
N
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892-1858, USA.
Chan
C C
CC
Whitcup
S M
SM
Nussenblatt
R B
RB
Mochizuki
M
M
D000287:Administration, Topical; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000473:pathology; D001082:Aqueous Humor / Q000737:chemistry; D015815:Cell Adhesion Molecules / Q000032:analysis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins; D005136:Eye Proteins / Q000032:analysis; D005260:Female; D007124:Immunoenzyme Techniques; D009883:Ophthalmic Solutions; D051381:Rats; D011917:Rats, Inbred Lew; D012486:Salmonella typhimurium; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
D015815:Cell Adhesion Molecules; D004731:Endotoxins; D005136:Eye Proteins; D009883:Ophthalmic Solutions; D016559:Tacrolimus