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 proinflammatory/antiinflammatory 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 C. albicans (NCPF 3179, Bioball (TM) 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-1 beta, IL-6, IL-8, IL-10, IL-12p70 and TNF-alpha in THP-1 cells stimulated by C. albicans were determined by Cytometric Bead Array (CBA). Miconazole, clotrimazole, ketoconazole, and fluconazole exhibited antifungal activity against C. albicans Multishot 10E8 with a 8, 16, 64, and 128 mu g/ml MIC value. The azole antifungals showed low cytotoxicity against THP-1 cell line (IC50>512 mu g/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-alpha.