Division of Hematology/Oncology, Duke University Medical Center, Durham, North Carolina, USA.
Pediatr Blood Cancer. 2011 Dec 15;57(7):1239-43. doi: 10.1002/pbc.23226. Epub 2011 Jun 16.
Hemophagocytic lymphohistiocytosis (HLH) is an immunodysregulatory disorder for which more effective treatments are needed. The macrolide rapamycin has immunosuppressive properties, making it an attractive candidate for controlling the aberrant T cell activation that occurs in HLH. To investigate its therapeutic potential, we used rapamycin to treat Lymphocytic Choriomeningitis Virus (LCMV)-infected perforin-deficient (Prf1(-/-)) mice according to a well-established model of HLH. At the regimens tested, rapamycin did not improve weight loss, splenomegaly, hemophagocytosis, cytopenias, or proinflammatory cytokine production in LCMV-infected Prf1(-/-) animals. Thus, single agent rapamycin appears ineffective in treating the clinical and laboratory manifestations of LCMV-induced HLH.
噬血细胞性淋巴组织细胞增生症（HLH）是一种免疫调节紊乱性疾病，需要更有效的治疗方法。大环内酯类雷帕霉素具有免疫抑制作用，使其成为控制 HLH 中异常 T 细胞激活的有吸引力的候选药物。为了研究其治疗潜力，我们根据已建立的 HLH 模型，使用雷帕霉素治疗细胞穿孔素缺陷（Prf1(-/-)）小鼠感染淋巴细胞脉络丛脑膜炎病毒（LCMV）。在测试的方案中，雷帕霉素并没有改善 LCMV 感染 Prf1(-/-)动物的体重减轻、脾肿大、噬血细胞现象、血细胞减少或促炎细胞因子的产生。因此，单一药物雷帕霉素似乎对治疗 LCMV 诱导的 HLH 的临床和实验室表现无效。
