The immunomodulator AS101 inhibits endotoxin-induced uveits in the rat

Purpose. AS101 ((ammonium trichloro(dioxyethelene-0-0′) tellurate) is a potent immunomodulator that augments cytokine production. The purpose of our experiments was to examine the effect of AS101 on endotoxin-induced uveitis (EIU). Methods. EIU was produced in male Lewis rats by injecting 100 μg of lipopolysaccharide into one footpad. At 24 and 2 hours prior to endotoxin injection, animals received intraperitoneal injections of AS101 or PBS as a control. In experiment #1, animals were treated with AS101 at a dose of 0.1 mg (n=4), 0.5 mg (n=3), and 1.0 mg (n=4) or PBS (n=4). 24 hours after endotoxin injection ocular inflammation was assessed by counting infiltrating inflammatory cells on histologic sections. In experiment #2, breakdown of the blood-aqueous barrier in animals treated with two injections of 1.0 mg of AS101 (n=6) or PBS (n=6) was assessed by performing cell counts and protein assays of aqueous humor. In experiment #3, serum TNF-α levels were determined by ELISA 2 hours after endotoxin injection in animals treated with two injections of 0.5mg AS101(n=6) or placebo (n=6). Results. AS101 significantly decreased the number of infiltrating inflammatory cells per histologic section (mean±SEM) in a dose-dependent fashion: 517.5±47.2 (0.1 mg), 188.7±49.5 (0.5 mg), 38.8±8.9 (1.0 mg), and 794.9±31.3 (PBS) (p<0.0001). Mean aqueous humor protein (mg/ml) and cell counts (cells/μl) were 31±0.6 and 5061.7±105.7 in animals treated with PBS and 12±0.8 and 677.6±175.5 in animals treated with AS101 (p<0.0001). Serum TNF-α levels were over twice as high in animals treated with AS101 than in PBS treated controls (p=0.0014), Conclusions. AS101 significantly inhibited inflammation and breakdown of the blood-aqueous barrier in EIU and may be useful in treating acute ocular inflammatory disease.