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Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis
INTRODUCTION: The purpose of this study was to determine if oral administration of the interleukin (IL) 12/IL-23 inhibitor, STA-5326, is effective in experimental autoimmune uveoretinitis (EAU). METHODS: C57BL/6J mice were immunised with human interphotoreceptor retinoid binding protein peptide (IRB...
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592812/ https://www.ncbi.nlm.nih.gov/pubmed/18847496 http://dx.doi.org/10.1186/ar2530 |
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author | Keino, Hiroshi Watanabe, Takayo Sato, Yasuhiko Niikura, Mamoru Wada, Yumiko Okada, Annabelle A |
author_facet | Keino, Hiroshi Watanabe, Takayo Sato, Yasuhiko Niikura, Mamoru Wada, Yumiko Okada, Annabelle A |
author_sort | Keino, Hiroshi |
collection | PubMed |
description | INTRODUCTION: The purpose of this study was to determine if oral administration of the interleukin (IL) 12/IL-23 inhibitor, STA-5326, is effective in experimental autoimmune uveoretinitis (EAU). METHODS: C57BL/6J mice were immunised with human interphotoreceptor retinoid binding protein peptide (IRBP(1–20)). STA-5326 at a dose of either 5 mg/kg or 20 mg/kg, or vehicle alone, was orally administered once a day for six days a week from day 0 to day 14. Fundus examination was performed on day 14 and day 18 after immunisation. Mice were euthanased on day 18 and the eyes were enucleated for histopathological examination. In vivo-primed draining lymph node cells were stimulated with IRBP(1–20 )and culture supernatant was harvested for assay of interferon (IFN)-γ and IL-17 by ELISA. Intracellular expression of IFN-γ and IL-17 in CD4(+ )T cells of cultured draining lymph node cells was assessed by flow cytometry. The level of IL-12 p40 in serum was examined in STA-5326-treated or vehicle-treated mice receiving immunisation. RESULTS: The level of IL-12 p40 in serum was decreased in mice treated with STA-5326. Oral administration of either 5 mg/kg or 20 mg/kg STA-5326 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. Although IFN-γ production of draining lymph node cells was increased in STA-5326-treated mice by ELISA analysis, the proportion of IFN-γ-producing cells was not significantly altered. However, IL-17 production and the proportion of IL-17-producing cells were significantly reduced in STA-5326-treated mice. Furthermore, oral administration of STA-5326 during the effector phase reduced the severity of EAU. 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. |
format | Text |
id | pubmed-2592812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-25928122008-12-03 Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis Keino, Hiroshi Watanabe, Takayo Sato, Yasuhiko Niikura, Mamoru Wada, Yumiko Okada, Annabelle A Arthritis Res Ther Research Article INTRODUCTION: The purpose of this study was to determine if oral administration of the interleukin (IL) 12/IL-23 inhibitor, STA-5326, is effective in experimental autoimmune uveoretinitis (EAU). METHODS: C57BL/6J mice were immunised with human interphotoreceptor retinoid binding protein peptide (IRBP(1–20)). STA-5326 at a dose of either 5 mg/kg or 20 mg/kg, or vehicle alone, was orally administered once a day for six days a week from day 0 to day 14. Fundus examination was performed on day 14 and day 18 after immunisation. Mice were euthanased on day 18 and the eyes were enucleated for histopathological examination. In vivo-primed draining lymph node cells were stimulated with IRBP(1–20 )and culture supernatant was harvested for assay of interferon (IFN)-γ and IL-17 by ELISA. Intracellular expression of IFN-γ and IL-17 in CD4(+ )T cells of cultured draining lymph node cells was assessed by flow cytometry. The level of IL-12 p40 in serum was examined in STA-5326-treated or vehicle-treated mice receiving immunisation. RESULTS: The level of IL-12 p40 in serum was decreased in mice treated with STA-5326. Oral administration of either 5 mg/kg or 20 mg/kg STA-5326 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. Although IFN-γ production of draining lymph node cells was increased in STA-5326-treated mice by ELISA analysis, the proportion of IFN-γ-producing cells was not significantly altered. However, IL-17 production and the proportion of IL-17-producing cells were significantly reduced in STA-5326-treated mice. Furthermore, oral administration of STA-5326 during the effector phase reduced the severity of EAU. 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. BioMed Central 2008 2008-10-13 /pmc/articles/PMC2592812/ /pubmed/18847496 http://dx.doi.org/10.1186/ar2530 Text en Copyright © 2008 Keino et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Keino, Hiroshi Watanabe, Takayo Sato, Yasuhiko Niikura, Mamoru Wada, Yumiko Okada, Annabelle A Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis |
title | Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis |
title_full | Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis |
title_fullStr | Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis |
title_full_unstemmed | Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis |
title_short | Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis |
title_sort | therapeutic effect of the potent il-12/il-23 inhibitor sta-5326 on experimental autoimmune uveoretinitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592812/ https://www.ncbi.nlm.nih.gov/pubmed/18847496 http://dx.doi.org/10.1186/ar2530 |
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