title: Protection against malaria by anti-erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites.
abstract: We have previously reported that erythropoiesis commences in the liver and spleen after malarial infection, and that newly generated erythrocytes in the liver are essential for infection of malarial parasites as well as continuation of infection. At this time, erythropoietin (EPO) is elevated in the serum. In the present study, we administered EPO or anti-EPO antibody into C57BL/6 (B6) mice to modulate the serum level of EPO. When mice were infected with a non-lethal strain (17NXL) of Plasmodium yoelii (blood-stage infection of 10(4) parasitized erythrocytes per mouse), parasitemia continued for 1 month, showing a peak at day 17. Daily injection of EPO (200 IU/day per mouse) from day five to day 14 prolonged parasitemia, whereas injection of anti-EPO antibody (1.5 mg/day per mouse) every second day from day five to day 28 decreased it. Erythropoiesis was confirmed in the liver, spleen and bone marrow by the appearance of nucleated erythrocytes (TER119+). When anti-EPO antibody was injected by the same protocol into mice infected with a lethal strain (17XL) of P. yoelii, all mice showed decreased parasitemia and recovered from the infection. These results suggest that the use of anti-EPO antibody after malarial infection may be of therapeutic value in severe cases of malaria.
authors.affiliation: Department of Immunology, Niigata University School of Medicine, Niigata, Japan.
authors.forename: Shyunsuke
authors.initials: S
authors.lastname: Tsubata
authors.forename: Kazuto
authors.initials: K
authors.lastname: Ebe
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kawamura
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Ishimoto
authors.forename: Chikako
authors.initials: C
authors.lastname: Tomiyama-Miyaji
authors.forename: Hisami
authors.initials: H
authors.lastname: Watanabe
authors.forename: Hiroho
authors.initials: H
authors.lastname: Sekikawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Aoyagi
authors.forename: Toru
authors.initials: T
authors.lastname: Abo
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000494:pharmacology; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood / Q000276:immunology*; D006801:Humans; D007167:Immunotherapy; D008099:Liver / Q000187:drug effects / Q000502:physiology*; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D010967:Plasmodium yoelii / Q000254:growth & development / Q000502:physiology
chemical_list: D000906:Antibodies; D004921:Erythropoietin