Effects of Antifungal Agents and Interferon on Macrophage Cytotoxicity for Fungi and Tumor Cells

Abstract

The activated macrophage may play a central role in host effector mechanisms against invading fungi. Here we demonstrate the importance of the activation state of murine macrophages for both fungistatic and fungicidal activity. Host factors such as γ interferon and microbial products such as endotoxin can interact synergistically to initiate this cytotoxicity. This activated state may be aided by antifungal agents such as amphotericin B. Both a methyl ester derivative of amphotericin Band liposomal amphotericin B potentiated macrophage activation but were less potent than amphotericin B. Other available antifungal agents such as azole compounds and flucytosine did not possess this ability to interact with the intrinsic macrophage effector mechanisms. However, ketoconazole and itraconazole avidly bind to macrophages as the biologically active drug. The azoleloading of macrophages may be a factor in macrophage cytotoxicity for fungi.