Recombinant human IFN-alpha inhibits cerebral malaria and reduces parasite burden in mice

Most C57BL/6 mice infected i.p. with Plasmodium berghei ANKA (PbA) die between 7 and 14 days with neurologic signs, and the remainder die later (>15 days) with severe anemia. Daily i.p. injections of a recombinant human IFN-alpha (active on mouse cells) prevented death by cerebral malaria (87% de...

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Published inJournal of Immunology Vol. 178; no. 10; pp. 6416 - 6425
Main Authors Vigário, Ana Margarida, Belnoue, Elodie, Grüner, Anne Charlotte, Mauduit, Marjorie, Kayibanda, Michèle, Deschemin, Jean-Christophe, Marussig, Myriam, Snounou, Georges, Mazier, Dominique, Gresser, Ion, Rénia, Laurent
Format Journal Article
LanguageEnglish
Published United States 15.05.2007
Subjects
Anemia - immunology
Anemia - parasitology
Anemia - pathology
Animals
Female
Humans
Injections, Intraperitoneal
Interferon Type I - administration & dosage
Interferon Type I - therapeutic use
Malaria, Cerebral - immunology
Malaria, Cerebral - parasitology
Malaria, Cerebral - pathology
Malaria, Cerebral - prevention & control
Mice
Mice, Inbred C57BL
Parasitemia - drug therapy
Parasitemia - immunology
Parasitemia - pathology
Plasmodium berghei
Plasmodium berghei - drug effects
Plasmodium berghei - immunology
Recombinant Proteins
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Summary:Most C57BL/6 mice infected i.p. with Plasmodium berghei ANKA (PbA) die between 7 and 14 days with neurologic signs, and the remainder die later (>15 days) with severe anemia. Daily i.p. injections of a recombinant human IFN-alpha (active on mouse cells) prevented death by cerebral malaria (87% deaths in the control mice vs 6% in IFN-alpha-treated mice). The mechanisms of this IFN-alpha protective effect were multiple. IFN-alpha-treated, PbA-infected mice showed 1) a marked decrease in the number of PbA parasites in the blood mediated by IFN-gamma, 2) less sequestered parasites in cerebral vessels, 3) reduced up-regulation of ICAM-1 expression in brain endothelial cells, 4) milder rise of blood levels of TNF, 5) increased levels of IFN-gamma in the blood resulting from an increased production by splenic CD8+ T cells, and 6) fewer leukocytes (especially CD8+ T cells) sequestered in cerebral vessels. On the other hand, IFN-alpha treatment did not affect the marked anemia observed in PbA-infected mice. Survival time in IFN-alpha-treated mice was further increased by performing three blood transfusions over consecutive days.
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ISSN:0022-1767
1550-6606
1365-2567
DOI:10.4049/jimmunol.178.10.6416