Interleukin-3 induces antimicrobial activity against Leishmania amazonensis and Trypanosoma cruzi and tumoricidal activity in human peripheral blood-derived macrophages.
The ability of interleukin-3 (IL-3) to induce antimicrobial and tumoricidal activity was evaluated. Macrophages infected with two intracellular protozoa, Leishmania amazonensis or Trypanosoma cruzi, were treated with cytokines. IL-3 induced a dose-dependent enhancement of microbistasis against leishmanias, and the activity of IL-3 (100 ng/ml) was comparable to that of gamma interferon (IFN-gamma) (1,000 U/ml). In addition, IL-3 in combination with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or macrophage CSF (M-CSF) or with IFN-gamma reduced infection and lowered the required dose. IL-3 similarly activated macrophages to inhibit intracellular replication of T. cruzi. Furthermore, IL-3 induced antibody-independent tumoricidal activity against melanoma cells that was dose dependent and comparable to that of lipopolysaccharide and GM-CSF. The mechanisms by which IL-3 induced antimicrobial activity may involve at least the augmentation of oxidative capacity. IL-3, at concentrations of 0.5 ng/ml or greater, led to a significantly increased oxidative burst which paralleled the inhibition of protozoan replication. The enhancement of oxidative capacity by IL-3 (5 ng/ml or higher) was comparable to that of IFN-gamma. The induction of tumoricidal activity was associated with the production of tumor necrosis factor alpha (TNF-alpha), which in this system may feed back to enhance the macrophage inhibition of leishmanias, as demonstrated by neutralization of IL-3 activation by anti-TNF-alpha antibody. Thus, peripheral blood macrophages remain responsive to IL-3, as demonstrated by enhanced antimicrobial and tumoricidal activity. IL-3 may have potential clinical applications because of these properties and its effect on myelopoiesis.
Ho
J L
JL
Department of Medicine, Cornell University Medical College, New York, New York 10021.
Reed
S G
SG
Sobel
J
J
Arruda
S
S
He
S H
SH
Wick
E A
EA
Grabstein
K H
KH
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D007891:Leishmania / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007377:Interleukin-3; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor