Effect of cytokines on antifungal activity of human polymorphonuclear leucocytes against yeast cells of Paracoccidioides brasiliensis

Abstract

In our previous study, it was observed that human peripheral blood polymorphonuclear leucocytes (PMNs) exhibited a fungistatic effect on yeast cells of Paracoccidioides brasiliensis, and that interferon-γ (IFN-γ), but not tumor necrosis factor-α or interleukin-8 (IL-8), enhanced the antifungal activity of PMNs. In the present study, granulocyte-macrophage colony-stimulating factor (GM-CSF) also enhanced the PMN activity. GM-CSF-activated PMNs exhibited a killing effect on P. brasiliensis isolate Bt-4 and an enhanced fungistatic effect on isolate Aoki. IL-1β activated PMNs to kill isolate Bt-4. Granulocyte colony-stimulating factor had no effect. Combinations of IFN-γ with GM-CSF or IL-1β, but not a combination of GM-CSF and IL-1β, exhibited a synergistic effect in enhancing the antifungal activity of PMNs. These results strongly suggest that PMNs activated with IFN-γ, GM-CSF and/or IL-1β might play an important role in host defense in early infection with P. brasiliensis due to their enhanced antifungal activity.