title: Erythropoietin protects against murine cerebral malaria through actions on host cellular immunity.
abstract: Cerebral malaria (CM) is associated with excessive host proinflammatory responses and endothelial activation. The hematopoietic hormone erythropoietin (EPO) possesses neuroprotective functions in animal models of ischemic-hypoxic, traumatic, and inflammatory injuries. In the Plasmodium berghei ANKA model of experimental CM (ECM), recombinant human EPO (rhEPO) has shown evident protection against ECM. To elucidate the mechanism of EPO in this ECM model, we investigated the effect of rhEPO on host cellular immune responses. We demonstrated that improved survival of mice with ECM after rhEPO treatment was associated with reduced endothelial activation and improved integrity of the blood-brain barrier. Our results revealed that rhEPO downregulated the inflammatory responses by directly inhibiting the levels and functions of splenic dendritic cells. Conversely, rhEPO treatment led to significant expansion of regulatory T cells and increased expression of the receptor cytotoxic T lymphocyte antigen 4 (CTLA-4). The data presented here provide evidence of the direct effect of rhEPO on host cellular immunity during ECM.
authors.affiliation: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wei
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Sun
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Zhu
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Feng
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Shang
authors.forename: Liwang
authors.initials: L
authors.lastname: Cui
authors.forename: Yaming
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D060908:CTLA-4 Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects*; D016779:Malaria, Cerebral / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010962:Plasmodium berghei; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
chemical_list: D060908:CTLA-4 Antigen; D016207:Cytokines; D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin