Du Yunting, Chen Guang, Zhang Xuexing, Yu Chunyun, Cao Yaming, Cui Liwang
Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, China.
Department of Parasitology, College of Basic Medical Sciences, Jiamusi University, Jiamusi, China.
Int Immunopharmacol. 2017 Jul;48:219-230. doi: 10.1016/j.intimp.2017.05.008. Epub 2017 May 19.
Cerebral malaria (CM) is a severe neurological syndrome in humans and the main fatal cause of malaria. In malaria epidemic regions, despite appropriate anti-malarial treatment, 10-20% of deaths still occur during the acute phase. This is largely attributable to poor treatment access, therapeutic complexity and drug resistance; thus, developing additional clinical adjunctive therapies is an urgent necessity. In this study, we investigated the effect of artesunate (AST) and recombinant human erythropoietin (rhEPO) using an experimental cerebral malaria (ECM) model-C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). Treatment with the combination of AST and rhEPO reduced endothelial activation and improved the integrity of blood brain barrier, which led to increased survival rate and reduced pathology in the ECM. In addition, this combination treatment down-regulated the Th1 response during PbA infection, which was correlated with the reduction of CCL2, TNF-α, IFN-γ, IL-12, IL-18, CXCL9 and CXCL10 levels, leading to reduced accumulation of pathogenic T cells in the brain. Meanwhile, AST and rhEPO combination led to decreased maturation and activation of splenic dendritic cells, expansion of regulatory T cells, and increased IL-10 and TGF-β production. In conclusion, these data provide a theoretical basis for clinical adjunct therapy with rhEPO and AST in human cerebral malaria patients.
脑型疟疾（CM）是人类一种严重的神经综合征，也是疟疾的主要致死原因。在疟疾流行地区，尽管进行了适当的抗疟治疗，但仍有10%-20%的患者在急性期死亡。这在很大程度上归因于治疗可及性差、治疗复杂性和耐药性；因此，开发额外的临床辅助治疗迫在眉睫。在本研究中，我们使用实验性脑型疟疾（ECM）模型——感染伯氏疟原虫ANKA（PbA）的C57BL/6小鼠，研究了青蒿琥酯（AST）和重组人促红细胞生成素（rhEPO）的作用。AST和rhEPO联合治疗可降低内皮细胞活化，改善血脑屏障的完整性，从而提高ECM小鼠的存活率并减轻病理变化。此外，这种联合治疗下调了PbA感染期间的Th1反应，这与CCL2、TNF-α、IFN-γ、IL-12、IL-18、CXCL9和CXCL10水平的降低相关，导致致病性T细胞在脑中的积聚减少。同时，AST和rhEPO联合治疗导致脾树突状细胞的成熟和活化减少、调节性T细胞扩增以及IL-10和TGF-β产生增加。总之，这些数据为rhEPO和AST用于人类脑型疟疾患者的临床辅助治疗提供了理论依据。
