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

In our previous study, it was observed that human peripheral blood polymorp honuclear leucocytes (PMNs) exhibited a fungistatic effect on yeast cells o f Paracoccidioides brasiliensis, and that interferon-gamma (IFN-gamma), but not tumor necrosis factor-alpha or interleukin-8 (IL-8), enhanced the anti fungal activity of PMNs. In the present study, granulocyte-macrophage colon y-stimulating factor (GM-CSF) also enhanced the PMN activity. GM-CSF-activa ted PMNs exhibited a killing effect on P. brasiliensis isolate Bt-4 and an enhanced fungistatic effect on isolate Aoki. IL-1 beta activated PMNs to ki ll isolate Bt-4. Granulocyte colony-stimulating factor had no effect. Combi nations of IFN-gamma with GM-CSF or IL-1 beta, but not a combination of GM- CSF and IL-1 beta, exhibited a synergistic effect in enhancing the antifung al activity of PMNs. These results strongly suggest that PMNs activated wit h IFN-gamma, GM-CSF and/or IL-1 beta might play an important role in host d efense in early infection with P. brasiliensis due to their enhanced antifu ngal activity.