Granulocyte-macrophage and macrophage colony-stimulating factors activate intramacrophage killing of Leishmania mexicana amazonensis.
Leishmania organisms are important pathogens, causing diseases worldwide. Standard therapies are often toxic and are not always effective. The effect of recombinant human granulocyte-macrophage and macrophage colony-stimulating factors (GM-CSF and M-CSF) on intramacrophage survival of Leishmania mexicana amazonensis (Lma) were compared with those of interferon-gamma (IFN-gamma). Macrophages previously infected with Lma were treated with or without GM-CSF and M-CSF. Compared with no cytokine treatment, treatment with GM-CSF (0.1-100 ng/ml) or M-CSF (1:3.5 X 10(6) - 1:3.5 X 10(3) dilutions) caused a significant dose-dependent reduction in intracellular parasites, 427 +/- 20 (mean +/- SE) Lma/100 macrophages. GM-CSF or M-CSF in combination with IFN-gamma resulted in more effective inhibition of intracellular parasites. Thus, the cytostatic activity appears to require interaction between cytokines, macrophages, and amastigotes. These cytokines are potential therapeutic agents for visceral leishmaniasis.
Ho
J L
JL
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Reed
S G
SG
Wick
E A
EA
Giordano
M
M
D000818:Animals; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003470:Culture Media; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007894:Leishmania mexicana / Q000276:immunology*; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology*; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D003470:Culture Media; D006133:Growth Substances; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor