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 hierarchy of inhibitory activity was observed, where itraconazole was greater than ketoconazole greater than miconazole greater than 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.