Effects of Cytokines and Fluconazole on the Activity of Human Monocytes against Candida albicans

Abstract

ABSTRACT This study evaluates the effects of cytokines, used singly and in combination, on the microbicidal activity of human monocyte-derived macrophages (MDM) against intracellular Candida albicans in the presence and absence of fluconazole. In the absence of fluconazole, the addition of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), gamma interferon (IFN-γ), or IL-4 had no effect on the growth of C. albicans . In contrast, the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in decreased growth ( P < 0.05), while the addition of IL-10 resulted in increased growth ( P < 0.01). In the presence of fluconazole, only the addition of IFN-γ resulted in an increase in the growth of C. albicans . In the presence or absence of fluconazole, all cytokine combinations except IFN-γ plus GM-CSF caused significant decreases in growth ( P < 0.01). IL-10 and IL-4 did not influence the activity of TNF-α or IL-1β. In the absence or presence of C. albicans the addition of fluconazole, all of the cytokines studied, and combinations of fluconazole and selected cytokines caused increases in nitric oxide (NO) production ( P < 0.01). Similar observations were made for superoxide (O 2 − ) only in the presence of C. albicans . The greatest concentrations of NO and O 2 − were produced when C. albicans alone was present in the assays. Our results demonstrate that in the presence of low concentrations of fluconazole (0.1 times the MIC), selected cytokines and their combinations significantly increase the microbicidal activity of MDM against intracellular C. albicans .