title: Recombinant human IFN-alpha inhibits cerebral malaria and reduces parasite burden in mice.
abstract: 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.
authors.affiliation: Institut Cochin, Département d'Immunologie, Paris, France.
authors.forename: Ana Margarida
authors.initials: AM
authors.lastname: Vigário
authors.forename: Elodie
authors.initials: E
authors.lastname: Belnoue
authors.forename: Anne Charlotte
authors.initials: AC
authors.lastname: Grüner
authors.forename: Marjorie
authors.initials: M
authors.lastname: Mauduit
authors.forename: Michèle
authors.initials: M
authors.lastname: Kayibanda
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Deschemin
authors.forename: Myriam
authors.initials: M
authors.lastname: Marussig
authors.forename: Georges
authors.initials: G
authors.lastname: Snounou
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: Ion
authors.initials: I
authors.lastname: Gresser
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
mesh_terms: D000740:Anemia / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D000818:Animals; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007370:Interferon Type I / Q000008:administration & dosage* / Q000627:therapeutic use; D016779:Malaria, Cerebral / Q000276:immunology* / Q000469:parasitology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018512:Parasitemia / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D010962:Plasmodium berghei / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins
chemical_list: D007370:Interferon Type I; D011994:Recombinant Proteins