Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitis
Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitis
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DOI：
10.1097/00054725-200405000-00002
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发表时间：
2004-05-01
影响因子：
4.9
通讯作者：
Matsuda, H
中科院分区：
文献类型：
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作者：
Mizushima, T;Ito, T;Matsuda, H
背景：FTY720是一种具有较强免疫抑制活性的新型试剂。FTY720诱导的免疫抑制是通过与传统免疫抑制剂完全不同的机制实现的，即通过改变淋巴细胞的组织分布而不是抑制激活。在本研究中，我们观察了FTY720对白细胞介素10基因缺陷(IL-10(-/-))小鼠慢性结肠炎的疗效。结果：FTY720单次给药后，循环中的淋巴细胞在次级淋巴组织中被隔离。结论：FTY720对IL-10(-/-)小鼠结肠炎有明显的治疗作用，其作用机制可能是通过减少结肠黏膜中淋巴细胞的数量，减少干扰素-γ的产生而实现的。
Background: FTY720 is a novel reagent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY720 is mediated by completely different mechanisms from those of conventional immunosuppressants, that is, by altering the tissue distribution of lymphocytes rather than inhibiting activation. In this study, we examined the efficacy of FTY720 in the treatment of chronic colitis in an interleukin-10 gene-deficient (IL-10(-/-)) mouse model.Methods: FTY720 was administered orally for 4 weeks to IL-10(-/-) mice with clinical signs of colitis. The gross and histologic appearance of the colon and the numbers, phenotype, cytokine production, and apoptosis of lymphocytes were compared with those characteristics in a control group.Results: Single-dose administration of FTY720 resulted in the sequestration of circulating lymphocytes within the secondary lymphoid tissues. Four-week administration resulted in a significant reduction of the CD4(+) T lymphocytes subpopulation in the colonic lamina propria and IFN-gamma production of the colonic lymphocytes, accompanied by a significant decrease in the severity of colitis.Conclusions: Treatment of established colitis in IL-10(-/-) mice with FTY720 ameliorated the colitis, probably as a result of decreasing the number of lymphocytes in the colonic mucosa and an associated reduction in IFN-gamma production.