In vitro effects of fluconazole (UK-49,858) and ketoconazole on mouse lymphocyte proliferation and on Candida blastospore destruction by human polymorphonuclear leukocytes.
The effects of fluconazole, a novel antifungal compound with a bis-triazole structure, were compared with those of ketoconazole on mitogen-induced DNA synthesis by cultured mouse lymphocytes, and on the destruction of fungal (Candida albicans) blastospores by human polymorphonuclear leukocytes. Fluconazole had little or no effect on concanavalin A- or lipopolysaccharide-induced lymphocyte proliferation at concentrations at which ketoconazole caused marked inhibition of the response to both these mitogens. Similarly, fungal cell killing by polymorphonuclear leukocytes was substantially depressed by ketoconazole but was unaffected by fluconazole. In addition, therefore, to having excellent in vivo antifungal activity, fluconazole, unlike ketoconazole, has been shown to have no inhibitory effect in two in vitro assays of immune function.
Senior
D S
DS
Pfizer Central Research, Pfizer Ltd, Kent, U.K.
Shaw
J T
JT
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015725:Fluconazole; D006801:Humans; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D013172:Spores, Fungal / Q000276:immunology; D014230:Triazoles / Q000494:pharmacology*
D000935:Antifungal Agents; D014230:Triazoles; D015725:Fluconazole; D007654:Ketoconazole