Granulocyte-macrophage colony-stimulating factor: involvement in control of Trypanosoma cruzi infection in mice.
Several cytokines play crucial roles in Trypanosoma cruzi infection in mice, but the involvement of endogenous granulocyte-macrophage colony-stimulating factor (GM-CSF) is poorly documented. This report shows that T. cruzi infection of mice triggered an early and sharp increase in plasma GM-CSF during the ascending phase of parasitemia. The plasma GM-CSF concentration remained stable at the peak of parasitemia and subsequently increased in those mice that survived to the acute phase. GM-CSF level increased again sharply, while parasitemia was rapidly decreasing. Finally, GM-CSF was undetectable, soon after the disappearance of circulating parasites. Injection of T. cruzi-infected mice with neutralizing anti-GM-CSF monoclonal antibodies induced the early appearance of parasitemia and aggravated cumulative mortality. In contrast, recombinant mouse GM-CSF (rmGM-CSF) caused sharp decreases in both parasitemia and cumulative mortality in T. cruzi-infected mice. Peritoneal macrophages from rmGM-CSF-treated and infected or uninfected mice were less infected ex vivo than those from control mice. Taken together these data demonstrate the protective action of endogenous GM-CSF in T. cruzi infection. Neutralization of endogenous GM-CSF aggravates infection, while exogenous rmGM-CSF decreases both parasitemia and host mortality.
Olivares Fontt
E
E
Laboratoire d'Immunologie Expérimentale, Faculté de Médecine, Université Libre de Bruxelles, Belgium.
Heirman
C
C
Thielemans
K
K
Vray
B
B
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood / Q000627:therapeutic use*; D008264:Macrophages / Q000382:microbiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000627:therapeutic use
D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor