Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.

<h4>Purpose</h4>To investigate the efficacy of leflunomide in experimental autoimmune uveitis (EAU) in rats.<h4>Methods</h4>Lewis rats were immunized with interphotoreceptor retinoid-binding peptide (IRBP) in order to generate EAU. Rats received three dose of leflunomide thro...

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Autores principales:	Cheng-bo Fang, De-xi Zhou, Shu-xiang Zhan, Yong He, Zhen Lin, Cheng Huang, Jun Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/756f84ab1d6a4d858e3ce2075abe1c74
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spelling	oai:doaj.org-article:756f84ab1d6a4d858e3ce2075abe1c742021-11-18T07:48:20ZAmelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.1932-620310.1371/journal.pone.0062071https://doaj.org/article/756f84ab1d6a4d858e3ce2075abe1c742013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23626769/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Purpose</h4>To investigate the efficacy of leflunomide in experimental autoimmune uveitis (EAU) in rats.<h4>Methods</h4>Lewis rats were immunized with interphotoreceptor retinoid-binding peptide (IRBP) in order to generate EAU. Rats received three dose of leflunomide through intragastric administration (prevention or treatment protocols) after immunization at three separate doses (3 mg/kg/d; 6 mg/kg/d; 12 mg/kg/d). Cyclosporin A was administered as a positive) control. Rats were euthanized during peak disease activity (day 14 or 15). Treatment effectiveness was evaluated in vivo using clinical EAU scoring (d14) and histopathological evaluation of enucleated eyes after experimental termination. The expression levels of inflammatory cytokines in the serum were quantified by ELISA. Eyeball of rats were harvested and mRNA expression of interleukin 17 (IL17) and IFN-γ were quantified through RT-PCR. Intracellular expression of interleukin (IL)-17 in the activated CD4(+) T cells was assessed by flow cytometry. The effects of leflunomide inhibition on immune responses in rats were investigated in isolated lymphocytes.<h4>Results</h4>Histopathological and clinical data revealed severe intraocular inflammation in the immunized rat. Inflammation reached its peak on day 14 in this EAU model. Treatment with leflunomide significantly prevented and treated EAU-induced ocular inflammation and decreased clinical and pathological scores compared to vehicle-treated eyes. Gene expression of IL17 and IFN-γ was markedly reduced in leflunomide-treated eyes. Leflunomide significantly decreased the serum levels of IL17 and IFN-γ. The study of IL17+ T cells in peripheral blood and spleen by flow cytometry showed a decreased number of Th17 cell in rats of leflunomide prevented group. Lymphocytes from animals treated with leflunomide had decreased antigen-specific proliferation in vitro compared with lymphocytes from untreated animals.<h4>Conclusions</h4>Oral administration of leflunomide effectively suppressed IRBP-induced uveitis in rats. These results suggest that leflunomide may be potentially clinical application in uveitis.Cheng-bo FangDe-xi ZhouShu-xiang ZhanYong HeZhen LinCheng HuangJun LiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e62071 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Cheng-bo Fang De-xi Zhou Shu-xiang Zhan Yong He Zhen Lin Cheng Huang Jun Li Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.
description	<h4>Purpose</h4>To investigate the efficacy of leflunomide in experimental autoimmune uveitis (EAU) in rats.<h4>Methods</h4>Lewis rats were immunized with interphotoreceptor retinoid-binding peptide (IRBP) in order to generate EAU. Rats received three dose of leflunomide through intragastric administration (prevention or treatment protocols) after immunization at three separate doses (3 mg/kg/d; 6 mg/kg/d; 12 mg/kg/d). Cyclosporin A was administered as a positive) control. Rats were euthanized during peak disease activity (day 14 or 15). Treatment effectiveness was evaluated in vivo using clinical EAU scoring (d14) and histopathological evaluation of enucleated eyes after experimental termination. The expression levels of inflammatory cytokines in the serum were quantified by ELISA. Eyeball of rats were harvested and mRNA expression of interleukin 17 (IL17) and IFN-γ were quantified through RT-PCR. Intracellular expression of interleukin (IL)-17 in the activated CD4(+) T cells was assessed by flow cytometry. The effects of leflunomide inhibition on immune responses in rats were investigated in isolated lymphocytes.<h4>Results</h4>Histopathological and clinical data revealed severe intraocular inflammation in the immunized rat. Inflammation reached its peak on day 14 in this EAU model. Treatment with leflunomide significantly prevented and treated EAU-induced ocular inflammation and decreased clinical and pathological scores compared to vehicle-treated eyes. Gene expression of IL17 and IFN-γ was markedly reduced in leflunomide-treated eyes. Leflunomide significantly decreased the serum levels of IL17 and IFN-γ. The study of IL17+ T cells in peripheral blood and spleen by flow cytometry showed a decreased number of Th17 cell in rats of leflunomide prevented group. Lymphocytes from animals treated with leflunomide had decreased antigen-specific proliferation in vitro compared with lymphocytes from untreated animals.<h4>Conclusions</h4>Oral administration of leflunomide effectively suppressed IRBP-induced uveitis in rats. These results suggest that leflunomide may be potentially clinical application in uveitis.
format	article
author	Cheng-bo Fang De-xi Zhou Shu-xiang Zhan Yong He Zhen Lin Cheng Huang Jun Li
author_facet	Cheng-bo Fang De-xi Zhou Shu-xiang Zhan Yong He Zhen Lin Cheng Huang Jun Li
author_sort	Cheng-bo Fang
title	Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.
title_short	Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.
title_full	Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.
title_fullStr	Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.
title_full_unstemmed	Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.
title_sort	amelioration of experimental autoimmune uveitis by leflunomide in lewis rats.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/756f84ab1d6a4d858e3ce2075abe1c74
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Amelioration of experimental autoimmune uveitis by leflunomide in Lewis rats.

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