May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Therapeutic Effect of the IL-12/IL-23 Inhibitor STA5326 in Experimental Autoimmune Uveoretinitis
Author Affiliations & Notes
  • H. Keino
    Kyourin Univ Sch of Med, Mitaka city, Japan
    Ophthalmology,
  • M. Niikura
    Kyourin Univ Sch of Med, Mitaka city, Japan
    Institute of Laboratory Animals,
  • Y. Wada
    Synta Pharmaceuticals Corp, Lexington, Massachusetts
  • A. A. Okada
    Kyourin Univ Sch of Med, Mitaka city, Japan
    Ophthalmology,
  • Footnotes
    Commercial Relationships  H. Keino, None; M. Niikura, None; Y. Wada, None; A.A. Okada, None.
  • Footnotes
    Support  Grant 19791293 from Japan society for the promotion of science
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2530. doi:https://doi.org/
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To determine whether oral administration of the IL-12/IL-23 inhibitor STA5326 is effective in suppressing inflammation in experimental autoimmune uveoretinitis (EAU).

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: uveitis-clinical/animal model • immunomodulation/immunoregulation • autoimmune disease 
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