Effect of Artesunate on Endotoxin-Induced Uveitis in Rats

PURPOSE. The purpose of this study was to explore the effect of artesunate on endotoxin-induced uveitis (EIU) in rats. METHODS. EIU was induced in male Long-Evans rats by footpad injection of lipopolysaccharide (LPS 200 mu g in 0.1 mL PBS; LPS-only group [LG]). PBS (0.1 mL), prednisolone (10 mg/kg in 0.1 mL PBS; prednisolone group [PG]), and artesunate of three concentrations (1, 10, 100 mg/kg; artesunate groups A, B, C [AGA, AGB, AGC]; all in 0.1 mL of PBS) were injected intravenously, respectively, 1 hour after LPS injection. Twenty-four hours after LPS injection, infiltrating cells and protein concentration in the aqueous humor, as well as tumor necrosis factor (TNF)-alpha, nitric oxide (NO), prostaglandin E2 (PGE2), and monocyte chemoattractant protein (MCP)-1, were measured. RESULTS. Rats in AGA did not have significant difference in infiltrating cell number (61.6 X 10(5) cells/mL; range, 20.0-147.8 cells/mL; P = 0.287), protein concentration (48.0 mg/mL; range, 18.0-101.8 mg/mL; P = 0.349), NO concentration (86.9 mu M/L; range, 30.5-192.5 mu M/L; P = 0.363), but had significant difference in TNF-alpha (1144.3 pg/mL; range, 460.0-1840.0 pg/mL; P = 0.038), PGE2 (12.8 ng/mL; range, 4.8-27.2 ng/mL; P = 0.005), and MCP-1 (6136 pg/mL; range, 20.0-147.8 pg/mL; P = 0.009) with those of LG. Artesunate at 10 mg/kg and 100 mg/kg significantly suppressed the infiltrating cells, protein concentration, TNF-alpha, NO, PGE2, and MCP-1 in the aqueous humor induced by LPS (P = 0.011-0.000). CONCLUSIONS. Dose-dependent decreases of infiltrating cells, protein concentration, TNF-alpha, PGE2, NO, and MCP-1 in the aqueous humor by artesunate treatment after LPS injection indicate that artesunate can suppress the inflammation of EIU by inhibiting the production of inflammatory mediators. (Invest Ophthalmol Vis Sci. 2011;52:916-919) DOI:10.1167/iovs.10-5892