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% 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.
Vigário
Ana Margarida
AM
Institut Cochin, Département d'Immunologie, Paris, France.
Belnoue
Elodie
E
Grüner
Anne Charlotte
AC
Mauduit
Marjorie
M
Kayibanda
Michèle
M
Deschemin
Jean-Christophe
JC
Marussig
Myriam
M
Snounou
Georges
G
Mazier
Dominique
D
Gresser
Ion
I
Rénia
Laurent
L
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
D007370:Interferon Type I; D011994:Recombinant Proteins