Interleukin-4 inhibits human macrophage activation by tumor necrosis factor, granulocyte-monocyte colony-stimulating factor, and interleukin-3 for antileishmanial activity and oxidative burst capacity.
Interleukin (IL)-4 has been implicated in the pathogenesis of leishmaniasis in a murine model. Experiments were done to examine the effect of IL-4 on cytokine activation of macrophages. Interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF alpha), and IL-3 activate macrophages to inhibit replication of leishmaniae. IL-4 abrogated in a dose- and time-dependent manner the induction of antileishmanial activity by these cytokines. The depression of oxidative burst capacity is one mechanism by which IL-4 inhibits macrophage activation. IL-4 diminished in a dose- and time-dependent manner the TNF alpha enhancement of oxidative capacity. Pretreatment with IL-4 for 48, 24, or 0 h, respectively, inhibited the generation of superoxide induced by TNF alpha by 90%, 60%, and 40%. Furthermore, IL-4 abrogated the enhancement of oxidative capacity by IFN-gamma, GM-CSF, and IL-3. These data suggest that IL-4 is a potent deactivator of macrophage antimicrobial functions and may contribute to the pathogenesis of visceral leishmaniasis.
Ho
J L
JL
Division of International Medicine, Cornell University Medical College, New York, New York 10021.
He
S H
SH
Rios
M J
MJ
Wick
E A
EA
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D007891:Leishmania / Q000276:immunology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000469:parasitology; D009000:Monocytes / Q000469:parasitology; D010084:Oxidation-Reduction; D010587:Phagocytosis; D016897:Respiratory Burst / Q000276:immunology*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007377:Interleukin-3; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor