Research Article

Immunology and Cell Biology (2005) 83, 638–642; doi:10.1111/j.1440-1711.2005.01385.x

Protection against malaria by anti-erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites

Shyunsuke Tsubata1,2, Kazuto Ebe2, Toshihiko Kawamura1, Yuiko Ishimoto2, Chikako Tomiyama-Miyaji1,3, Hisami Watanabe4, Hiroho Sekikawa1, Yutaka Aoyagi2 and Toru Abo1

  1. 1 Department of Immunology, Niigata University School of Medicine, Niigata, Japan
  2. 2 Third Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan
  3. 3 School of Health Sciences, Faculty of Medicine, Niigata University, Niigata, Japan
  4. 4 Center of Molecular Biosciences, University of the Ryukyus, Okinawa, Japan

Correspondence: Dr Toru Abo, Department of Immunology, Niigata University School of Medicine, Asahimachi-dori 1-757, Niigata 951-8510, Japan. Email: immunol2@med.niigata-u.ac.jp

Received 18 April 2005; Accepted 16 June 2005; Published online 21 October 2005.

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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 104 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.

Keywords:

antibody, anti-erythropoietin, erythropoietin, liver, malaria, parasitemia

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