TY - JOUR
T1 - Artesunate and erythropoietin synergistically improve the outcome of experimental cerebral malaria
AU - Du, Yunting
AU - Chen, Guang
AU - Zhang, Xuexing
AU - Yu, Chunyun
AU - Cao, Yaming
AU - Cui, Liwang
N1 - Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.intimp.2017.05.008
DO - 10.1016/j.intimp.2017.05.008
M3 - Article
C2 - 28531845
AN - SCOPUS:85019574834
SN - 1567-5769
VL - 48
SP - 219
EP - 230
JO - International Immunopharmacology
JF - International Immunopharmacology
ER -