IFN-gamma treatment of rodents infected with erythrocytic stages of Plasmodium chabaudi: differential effects according to the immunological status.
Recombinant rat interferon-gamma (rrIFN-gamma) was tested for its antimalarial activity in three different models of Plasmodium chabaudi-blood stage malaria. Doses ranging from 1 x 10(4) to 1 x 10(5) U of rrIFN-gamma were used in each model. In BALB/c mice (lethal infection), prophylactic treatment with daily intraperitoneal (i.p.) injections reduced parasitemia and delayed mortality. In contrast, subcutaneous administration of rrIFN-gamma was inefficient, as was curative schedule of i.p. administration. Euthymic Fischer rats, which develop an acute and resolutive infection, were partly protected by i.p. prophylactic administration of rrIFN-gamma. Parasitemia was reduced without being lengthened, resulting in a marked decrease in parasite burden. Subcutaneous administration was less efficient whereas curative schedule was not. Athymic (nude) Fischer rats which present a longlasting and stable infection were treated with prophylactic and curative schedules of i.p. administration of rrIFN-gamma. In each case, rrIFN-gamma-treated nude rats, as control nude rats, were unable to resolve their chronic infection. The conditions required to obtain a beneficial effect are thus restrictive for a therapeutic use in humans. Moreover, these results show that, despite the fact that IFN-gamma is considered as a major component of the immune response, this cytokine alone is not sufficient to induce the totality of the effector mechanisms necessary to cure malarial infections.
Watier
H
H
Centre d'Immunologie et de Biologie Parasitaire, INSERM U167, CNRS URA 624, Institut Pasteur, Lille, France.
Pancre
V
V
Lando
D
D
Capron
A
A
Auriault
C
C
D000818:Animals; D004912:Erythrocytes / Q000469:parasitology*; D007371:Interferon-gamma / Q000627:therapeutic use*; D008288:Malaria / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016788:Plasmodium chabaudi; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D007371:Interferon-gamma