Compared effects of azole antifungals on cytokine production of THP-1 cells activated by Candida albicans

Abstract

In this study we compared the cytotoxic and proinflamatory/antiinflamatory effects of azole antifungals such as clotrimazole, ketoconazole, miconazole and fluconazole on Candida albicans co-culture with THP-1 cell line. MICs of several azole antifungal agents were determined with Candida albicans (NCPF 3179, Bioball™ Multishot 10E8) by the broth microdilution plate method. Cytotoxic effects of antifungal drugs were evaluated on THP-1 cell line by WST-1 test. Cytokine levels of IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α in THP-1 cells stimulated by Candida albicans were determined by Cytometric Bead Array (CBA). Clotrimazole, ketoconazole, miconazole and fluconazole exhibited antifungal activity against Candida albicans Multishot 10E8 with a 16, 64, 8 and 128 µg/ml MIC value. The azole antifungals showed low cytotoxicity against THP-1 cell line (IC50>512 µg/ml). The results demonstrated that IL-8 levels were increased by azole antifungal drugs and particularly, clotrimazole significantly induced not only IL-8 but also TNF-α.