Invasive aspergillosis in mice immunosuppressed with cyclosporin A, tacrolimus (FK506), or sirolimus (rapamycin)
Invasive aspergillosis in mice immunosuppressed with cyclosporin A, tacrolimus (FK506), or sirolimus (rapamycin)
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DOI：
10.1093/infdis/175.1.222
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发表时间：
1997-01-01
影响因子：
6.4
通讯作者：
Washburn, RG
中科院分区：
文献类型：
--
作者：
High, KP;Washburn, RG
环孢菌素A、他克莫司和西罗莫司是免疫抑制剂，最初被描述为对曲霉属物种具有不同活性的抗真菌化合物。在远交CD-1小鼠中研究了用每种药剂处理的小鼠中侵袭性曲霉病的结果。从第-1天至第+14天单独给予免疫抑制剂或溶媒。在第0天通过侧尾静脉注射用静止的曲霉属分生孢子感染小鼠。大多数治疗方案的小鼠存活率明显高于用环孢素A治疗的小鼠（100 mg/kg/天;中位生存期，3天）：他克莫司，1 mg/kg/天（6.5天，P = .003）;西罗莫司，1或10 mg/kg/天（分别为7.5和9.5天; P = .002和.0001）;和单独媒介物（6.5天，P = 0.001），然而，用10 mg/kg/天他克莫司治疗的小鼠存活中位数为4.5天，10 mg西罗莫司组的存活率与单独给予溶媒的小鼠无差异（P = 0.55）。组织学评价表明，他克莫司和西罗莫司改善的存活率可能部分归因于直接的抗曲霉活性。
Cyclosporin A, tacrolimus, and sirolimus are immunosuppressive agents initially described as antifungal compounds with different activities for Aspergillus species. The outcome of invasive aspergillosis in mice treated with each agent was investigated in outbred CD-1 mice. Immunosuppressant or vehicle alone was administered from days -1 to +14. Mice were infected on day 0 with resting Aspergillus conidia via lateral tail vein injection. Survival was significantly greater with most regimens than for mice treated with cyslosporin A (100 mg/kg/day; median survival, 3 days): tacrolimus, 1 mg/kg/day (6.5 days, P = .003); sirolimus, 1 or 10 mg/kg/day (7.5 and 9.5 days, respectively; P = .002 and .0001); and vehicle alone (6.5 days, P = .001), However, mice treated with 10 mg/kg/day of tacrolimus survived a median of 4.5 days (P = .25), Survival in the 10-mg sirolimus group did not differ from that of mice given vehicle alone (P = .55), Histologic evaluation suggested the improved survival with tacrolimus and sirolimus may be due in part to direct anti-Aspergillus activity.