Effects of azole antifungals in vitro on host/parasite interactions relevant to Candida infections

Clotrimazole, fluconazole, itraconazole and ketoconazole were tested for their influence on three aspects of host/parasite interactions in the context of Candida infections. None of clotrimazole, itraconazole or ketoconazole had any effect on the adherence of C. albicans to vaginal epithelial cells, in vitro, regardless of whether the drugs were used to pretreat the fungi or the vaginal cells or were added to the fungus/vaginal cell mixture. Clotrimazole pretreatment of polymorphonuclear leucocytes led to a marked suppression of their ability to phagocytose and kill C. albicans, but fluconazole and ketoconazole had no similar effect. None of these three antifungals affected phagocytosis or killing when they were added to the leucocyte candida mixture or when used to pretreat the fungi. Clotrimazole and ketoconazole both reduced proliferative responses of lymphocyte suspensions to mitogens but fluconazole showed no anti-lymphocyte effect. This difference in action against lymphocytes may help to explain the known disparity between the antifungal effects of fluconazole and ketoconazole against C. albicans in vivo and against experimental candida infections in vitro. Clotrimazole effected a suppression of ATP concentrations in lymphocytes but fluconazole and ketoconazole had no similar effects.