Concurrent antiviral and immunosuppressive activities of leflunomide in vivo
Concurrent antiviral and immunosuppressive activities of leflunomide in vivo
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DOI：
10.1111/j.1600-6143.2005.01152.x
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发表时间：
2006-01-01
影响因子：
8.8
通讯作者：
Waldman, WJ
中科院分区：
文献类型：
--
作者：
Chong, AS;Zeng, H;Waldman, WJ
我们以前报道过，免疫抑制剂丙二腈酰胺类药物来氟米特和FK 778对巨细胞病毒（CMV）具有抗病毒活性。在目前的研究中，我们验证了来氟米特在CMV感染的心脏移植受者中同时发挥抗病毒活性和免疫抑制作用的假设。将Brown Norway心脏移植到刘易斯大鼠，然后接种大鼠CMV。空斑试验表明，来氟米特（30 mg/kg/天）使病毒载量降低4-6 log，并且病毒载量的降低不受尿苷给药的影响。来氟米特与环孢素A（CsA）或他克莫司在保存移植物完整性方面一样有效，直至第28天。这些研究直接证明了来氟米特的免疫抑制和抗病毒双重功能，增强了这种药物作为移植受体治疗的临床选择的前景。
We previously reported that the immunosuppressive malononitrileamides leflunomide and FK778 exert antiviral activity against cytomegalovirus (CMV). In the current investigation, we tested the hypothesis that leflunomide exerts concurrent antiviral activity and immune suppression in CMV-infected cardiac allograft recipients. Lewis rats were transplanted with Brown Norway hearts and then inoculated with rat CMV. Plaque assay demonstrated that leflunomide (30 mg/kg/day) reduced viral loads by 4-6 logs, and that the reduction in viral load was unaffected by administration of uridine. Leflunomide was as effective as cyclosporine A (CsA) or tacrolimus in preservation of allograft integrity through day 28. These studies directly demonstrate the bifunctionality of leflunomide as concurrently immunosuppressive and antiviral, enhancing the promise of this agent as a clinical option for treatment of transplant recipients.