COMPARISON OF THE IMMUNOSUPPRESSIVE ACTIVITIES OF THE ANTIMYCOTIC AGENTS ITRACONAZOLE, FLUCONAZOLE, KETOCONAZOLE AND MICONAZOLE ON HUMAN T-CELLS

Four antifungal agents have been screened in vitro for their immunosuppressive effects on proliferative responses in human mixed lymphocyte cultures (MLC). A hierachy of inhibitory activity was observed, where itraconazole was > ketoconazole > miconazole > fluconazole, with itraconazole as suppressive as cyclosporin A, and fluconazole completely without suppressive activity. The mechanism of inhibition did not involve blockade of T-cell growth factor production and, consistent with this, interleukin-2-dependent T-cell clone proliferation was blocked by these agents in the same order of decreasing activity as in MLC. The secretion of cytokines without known T-cell growth factor activity (interferon-gamma, tumour necrosis factor-alpha) was also not significantly blocked by these agents. These results therefore demonstrate that antifungal azole drugs may be variably strongly immunosuppressive for human T-lymphocyte proliferation in vitro, but none appear to be so via a mechanism involving inhibition of cytokine secretion.