S. Illinois Univ Edwardsville, Biological Sciences, Edwardsville, IL 62026-1651
The polyene antifungal Amphotericin B Squibb has been extensively studied for its effect on host immune responses mediated by T and B cells. Continuing thistradition, we have examined the ability of imidazole antifungal moleculesFluconazole (Diflucan)Pfizer and a derivative molecule Voriconazole (Vfend)Pfizer. These azoles inhibit cytochrome P450 and 14a-demethylase, an enzymeacting in the sterol pathway leading from lanosterol to ergosterol. Fluconazole is commonly used to treat infections by Candida species, while voriconazole has currently been approved for treating invasive aspergillosis and invasive candidiasis. Using a contact sensitizing assay with dinitrofluorobenzene (DNFB) described by Phauphak (J Immunol 112:115;1974) the effect of both imidazole drugs on DTH were determined.Fluconazole enhanced DTH response to DNFB at dosages from 1.0 to 6.0 mg. The optimal drug dosages and sensitizing time frame for drug exposure relative to DTH response was determined. Fluconazole also was found to reverse tolerization of mice to DNFB elicited by intravenous adminsitration of DNBSO3Kodak. The voriconazoleeffects on mouse DTH will be done in parallel to te fluconazole work, and we have found it to enhance DTH response.This work was supported in partby the Max Baer Heart Fund, FOE; and the LS-AMP Research Scholar's Program, NSF.
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