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H. Keino, M. Niikura, Y. Wada, A. A. Okada; Therapeutic Effect of the IL-12/IL-23 Inhibitor STA5326 in Experimental Autoimmune Uveoretinitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2530. doi: https://doi.org/.
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To determine whether oral administration of the IL-12/IL-23 inhibitor STA5326 is effective in suppressing inflammation in experimental autoimmune uveoretinitis (EAU).
C57BL/6J mice were immunized with human interphotoreceptor retinoid binding protein peptide (h-IRBP1-20). STA5326 at a dose of either 5 mg/kg or 20 mg/kg, or vehicle alone, was orally administered once a day, 6 days per week from day 0 to day 13. Fundus examination was performed on day 14 and day 18 after immunization. Mice were sacrificed on day 18 and eyes enucleated for histopathological examination. In vivo-primed draining lymph node cells were stimulated with h-IRBP1-20 and culture supernatant was harvested for assay of IFN-gamma and IL-17 by ELISA. Intracellular expression of IFN-gamma and IL-17 in CD4+ T cells was assessed by flow cytometry.
Oral administration of STA-5326 at both doses reduced the severity of EAU on day 14 and 18. In addition, mice treated with 20 mg/kg STA-5326 showed significantly decreased severity of EAU by histopathological analysis. IFN-gamma production was not significantly altered, however the production of IL-17 and the proportion of IL-17 producing cells were significantly reduced in STA-5326 treated mice.
These results indicate that oral administration of the IL-12/IL-23 inhibitor STA-5326 is effective in suppressing inflammation in the EAU model, and reduces the expansion of IL-17 producing cells. STA-5326 may represent a new therapeutic modality for human refractory uveitis.
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