Deferiprone, an orally deliverable iron chelator, ameliorates experimental autoimmune encephalomyelitis
Deferiprone, an orally deliverable iron chelator, ameliorates experimental autoimmune encephalomyelitis
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DOI：
10.1177/1352458507078916
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发表时间：
2007-11-01
影响因子：
5.8
通讯作者：
LeVine, S. M.
中科院分区：
文献类型：
--
作者：
Mitchell, K. M.;Dotson, A. L.;LeVine, S. M.
铁螯合剂Desferal可以抑制实验性自身免疫性脑脊髓炎（EAE）的疾病活动，这是一种多发性硬化症（MS）的动物模型，并已在MS的中试试验中进行了测试。口服铁螯合剂已经开发出来，克服了这些困难，本研究的目的是在EAE中测试口服螯合剂。将EAE活性的SJL小鼠随机分配给去铁素（150 mg/kg）或载药（水）2次/天灌胃。与EAE小鼠相比，给予去铁素的EAE小鼠的疾病活动性明显降低，炎症细胞浸润水平也较低（H&E染色显示）。t细胞浸润，通过抗cd3免疫组织化学染色评估，也减少了，尽管不明显。用含或不含250 μ M去铁蛋白的抗cd3和抗cd28刺激幼年SJL小鼠培养的脾细胞。不含去铁蛋白的共刺激脾细胞分裂率为39%，而含去铁蛋白的共刺激脾细胞分裂率为2.8%，后者的细胞存活率仅为前者的53%。去铁素对未共刺激的细胞的增殖和活力没有影响。综上所述，去铁素可有效抑制活动性EAE疾病并抑制t细胞功能。
The iron chelator, Desferal, suppressed disease activity of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), and it has been tested in pilot trials for MS. The administration regimen of Desferal is cumbersome and prone to complications. Orally-deliverable, iron chelators have been developed that circumvent these difficulties, and the objective of this study was to test an oral chelator in EAE. SJL mice with active EAE were randomly assigned to receive deferiprone (150 mg/kg) or vehicle (water) 2 x/day via gavage. EAE mice given deferiprone had significantly less disease activity and lower levels of inflammatory cell infiltrates (revealed by H&E staining) than EAE mice administered vehicle. T-cell infiltration, assessed by anti-CD3 immunohistochernical staining, also was reduced, although not significantly. Splenocytes cultured from naive SJL mice were stimulated with anti-CD3 and anti-CD28 with or without 250 mu M deferiprone. While similar to 39% of costimulated splenocytes without deferiprone underwent division, only similar to 2.8% of costimulated splenocytes with deferiprone divided and the latter cells were only 53% as viable as the former. Deferiprone had no effect on proliferation or viability of cells that were not costimulated. In summary, deferiprone effectively suppressed active EAE disease and it inhibited T-cell function.