Wang Fang, Tan Wenfeng, Guo Dunming, He Shaoheng
The Clinical Experiment Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
Eur J Pharmacol. 2007 Nov 14;573(1-3):230-40. doi: 10.1016/j.ejphar.2007.07.029. Epub 2007 Jul 24.
FTY720 belongs to a new class of immunosuppressants. Little is known about its influence on T cell subtypes and pathological changes in arthritis. Here we illustrated the effect of FTY720 on peripheral T cell subsets and joint damage of collagen-induced arthritis rats. Rats were administered FTY720 or prednisone daily from day 0 to day 28. Body weight, hind paw swelling and arthritis index were measured. Bone destruction was determined by micro-computed tomography and histopathology, and T cell subsets were analyzed by flow cytometry and immunohistochemistry. The results showed that FTY720 inhibited the development of arthritis. Radiological analysis revealed that FTY720 treated collagen-induced arthritic rats had much less joint damage in comparison to untreated collagen-induced arthritic rats. Histological study showed that collagen-induced arthritic rats suffered from inflammatory cell infiltration and synovial hyperplasia in their joints, and FTY720 treatment clearly reduced these pathological changes. Immunohistochemical analysis showed that FTY720 treatment significantly decreased the number of CD4(+) T cells in the synovium of collagen-induced arthritic rats. Collagen-induced arthritic rats appeared to have more CD4(+), but not CD8(+) T cells in their peripheral blood than normal control rats. Following FTY720 treatment, peripheral blood CD3(+) and CD4(+) T cells in collagen-induced arthritic rats were significantly decreased. In conclusion, FTY720 is an effective compound in the treatment of collagen-induced arthritic rats and in reducing CD4(+) T cells in collagen-induced arthritic rats.
FTY720属于一类新型免疫抑制剂。关于其对T细胞亚群的影响以及关节炎中的病理变化,人们了解甚少。在此,我们阐述了FTY720对胶原诱导性关节炎大鼠外周T细胞亚群及关节损伤的影响。从第0天至第28天,每天给大鼠施用FTY720或泼尼松。测量体重、后爪肿胀度和关节炎指数。通过微计算机断层扫描和组织病理学确定骨破坏情况,并通过流式细胞术和免疫组织化学分析T细胞亚群。结果表明,FTY720抑制关节炎的发展。放射学分析显示,与未治疗的胶原诱导性关节炎大鼠相比,接受FTY720治疗的胶原诱导性关节炎大鼠的关节损伤要少得多。组织学研究表明,胶原诱导性关节炎大鼠的关节存在炎性细胞浸润和滑膜增生,而FTY720治疗明显减轻了这些病理变化。免疫组织化学分析显示,FTY720治疗显著减少了胶原诱导性关节炎大鼠滑膜中CD4(+) T细胞的数量。胶原诱导性关节炎大鼠外周血中的CD4(+) T细胞似乎比正常对照大鼠更多,但CD8(+) T细胞并非如此。FTY720治疗后,胶原诱导性关节炎大鼠外周血中的CD3(+)和CD4(+) T细胞显著减少。总之,FTY720是治疗胶原诱导性关节炎大鼠以及减少胶原诱导性关节炎大鼠中CD4(+) T细胞的有效化合物。