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

Abstract

Interleukin (IL)-4 has been implicated in the pathogenesis ofleishmaniasis in a murine model. Experiments were done to examine the effect of IL-4 on cytokine activation of macrophages. Interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNFα), and IL-3 activate macrophages to inhibit replication ofleishmaniae. 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 TNFa enhancement ofoxidative capacity. Pretreatment with IL-4 for 48, 24, or 0 h, respectively, inhibited the generation of superoxide induced by TNFa by 90%, 60%, and 40%. Furthermore, IL-4 abrogated the enhancement of oxidative capacity by IFN-γ, 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.