Amelioration of Experimental Autoimmune Uveitis by Leflunomide in Lewis RatsReportar como inadecuado




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Purpose

To investigate the efficacy of leflunomide in experimental autoimmune uveitis EAU in rats.

Methods

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.

Results

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-γwas 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.

Conclusions

Oral administration of leflunomide effectively suppressed IRBP-induced uveitis in rats. These results suggest that leflunomide may be potentially clinical application in uveitis.



Autor: Cheng-bo Fang, De-xi Zhou, Shu-xiang Zhan, Yong He, Zhen Lin, Cheng Huang, Jun Li

Fuente: http://plos.srce.hr/



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