Effect of fluconazole on human polymorphonuclear leucocyte functions ex vivo against Candida albicans

Polymorphonuclear leucocytes (PMNs) are important components of host defenc e against fungi. We investigated the ex vivo effect of fluconazole on chemo taxis, adherence, superoxide anion (O-2(-)) generation and intracellular ki lling of Candida albicans blastoconidia after the administration of flucona zole (300 mg per os) to healthy volunteers. With regard to chemotaxis in re sponse to zymosan-activated serum (ZAS), as measured using an agarose gel t echnique, fluconazole neither increased, nor decreased the chemotaxis of PM Ns. The adherence was significantly enhanced after exposure of PMNs to fluc onazole under ex vivo conditions, whereas, O-2(-) production after stimulat ion of PMNs with ZAS was not affected by fluconazole. The effect of flucona zole on intracellular killing of C. albicans blastoconidia by PMNs was dete rmined by viable colony count, after release of yeast cells from disturbed neutrophils. Fluconazole under in vitro conditions, at a therapeutic concen tration, significantly increased the intracellular killing of C. albicans b y PMNs at 30 min when compared with the results obtained in ex vivo experim ents (p < 0.001). During 90 min of exposure, no significant difference was found between in vitro and ex vivo conditions (p > 0.05).