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Effects of topical FK506 on endotoxin-induced uveitis (EIU) in the Lewis rat
N Hikita1, C C Chan, S M Whitcup
1Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892-1858, USA.
Abstract:
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.
Insights
Topical FK506 (immunosuppressant) effectively reduced ocular inflammation in rats with endotoxin-induced uveitis (EIU). This macrolide antibiotic shows potential as an alternative treatment for anterior uveitis when steroids are contraindicated.
Area of Science:
- Ophthalmology
- Immunology
- Pharmacology
Background:
- FK506 is a macrolide antibiotic with potent immunosuppressive properties.
- Acute ocular inflammation, such as endotoxin-induced uveitis (EIU), poses a significant clinical challenge.
- Topical corticosteroids are standard treatment but have contraindications.
Purpose of the Study:
- To investigate the efficacy of topical FK506 in suppressing acute ocular inflammation.
- To evaluate the dose-dependent effect of FK506 on endotoxin-induced uveitis (EIU) in a rat model.
Main Methods:
- Lewis rats with EIU were treated with topical FK506 at 0.05% and 0.3% concentrations.
- Control groups received vehicle alone or 1% prednisolone acetate.
- Inflammatory cell counts in aqueous humor and histological inflammatory scores were assessed.
Main Results:
- Topical FK506 significantly decreased inflammatory cell counts and histological scores in a dose-dependent manner.
- 0.3% FK506 showed substantial reduction in inflammation compared to vehicle control.
- Systemic absorption of FK506 was minimal, indicating a localized ocular effect.
Conclusions:
- Topical FK506 demonstrates significant efficacy in suppressing acute ocular inflammation (EIU).
- FK506 may serve as a viable alternative therapy for anterior uveitis, particularly in patients unable to use topical steroids.