Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis.
GM-CSF induces three effects potentially beneficial in visceral leishmaniasis: blood monocyte mobilization, macrophage activation, and amelioration of granulocytopenia. To determine the experimental role and effect of GM-CSF in this intracellular infection, livers from Leishmania donovani-infected BALB/c mice were tested for GM-CSF mRNA expression and mice were treated with anti-GM-CSF antiserum or GM-CSF. L. donovani infection upregulated hepatic GM-CSF mRNA expression by 10-fold, and anti-GM-CSF treatment exacerbated visceral infection and tripled liver parasite burdens 4 wk after challenge. In euthymic mice with established infection, treatment with 1-5 micrograms/d murine GM-CSF induced three dose-related effects: peripheral blood leukocytosis, preferential accumulation of myelomonocytic cells at visceral foci of infection, and leishmanicidal activity comparable to that achieved by IFN-gamma. These effects were either largely or entirely T cell dependent. Treatment with human GM-CSF also induced anti-leishmanial activity but with little effect on peripheral leukocyte number or tissue myelomonocytic cell influx; human G-CSF stimulated marked peripheral granulocytosis and neutrophil tissue accumulation but induced little antileishmanial effect. These results identify a role for endogenous GM-CSF in the initial host defense response to L. donovani, reemphasize the influxing monocyte as an effector cell, and indicate that GM-CSF can be used as an antileishmanial treatment.
Murray
H W
HW
Division of Infectious Diseases, Cornell University Medical College, New York 10021.
Cervia
J S
JS
Hariprashad
J
J
Taylor
A P
AP
Stoeckle
M Y
MY
Hockman
H
H
D000818:Animals; D000906:Antibodies / Q000097:blood; D001483:Base Sequence; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D006099:Granuloma / Q000188:drug therapy; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000276:immunology*; D007964:Leukocytosis; D008099:Liver / Q000469:parasitology; D008262:Macrophage Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D013045:Species Specificity
D000906:Antibodies; D012333:RNA, Messenger; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor