Modulation of the course and outcome of blood-stage malaria by erythropoietin-induced reticulocytosis.
Severe anemia is a major life-threatening complication of malaria. The roles of erythropoietin (Epo) and erythropoiesis during blood-stage malaria were investigated. By treating Plasmodium chabaudi AS-infected C57BL/6 (B6) mice, which are resistant to malaria, with polyclonal anti-human Epo neutralizing antibody, we demonstrated that Epo-induced reticulocytosis was important for alleviating malarial anemia and for host survival. By inducing erythropoiesis in A/J mice, which are susceptible to malaria, and in B6 mice at various periods during infection, by use of exogenous recombinant murine Epo, untimely onset of reticulocytosis was shown to augment multiplication of parasites and result in lethal infection. However, timely inducement of reticulocytosis with Epo treatment alleviated malarial anemia and increased survival. Our data reveal the important role of Epo-induced reticulocytosis in modulating the course and outcome of blood-stage malaria. However, the mechanisms underlying the increased mortality associated with untimely treatment with Epo and the increased protection associated with timely treatment with Epo remain to be investigated.
Chang
Kai-Hsin
KH
Institute of Parasitology, McGill University, Macdonald Campus, Ste. Anne de Bellevue, Montreal General Hospital Research Institute, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4, Canada.
Tam
Mifong
M
Stevenson
Mary M
MM
D000818:Animals; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000627:therapeutic use*; D008288:Malaria / Q000097:blood / Q000628:therapy*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D016788:Plasmodium chabaudi; D011994:Recombinant Proteins; D045262:Reticulocytosis; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa