Imidazole effects on murine immune responses

• Published in: Microbial ecology in health and disease Vol. 20; no. 3; p. 159
• Main Authors: Kitz, D J, Bone, R, Purlee, S J, Freed, L, Bradstreet, T, Barton, J
• Format: Journal Article
• Language: English
• Published: 01.05.2008
• ISSN: 0891-060X; 1651-2235

Background: Antifungal molecules including amphotericin B CFungizone) Squibb are known to have profound effects on many aspects of host immune response. Our laboratory has extended this study to include two imidazole antifungal molecules: fluco-nazole (Diflucan) Pfizer and a derivative molecule voriconazole (Vfend) Pfizer. Both azole drugs inhibit cytochrome P450 and 14a-demethylase, an enzyme acting on fungal membrane sterols. Method: A contact sensitizing assay (J. Immunol 772:115, 1974) employing dinitrofluorobenzene (DNFB) Sigma belly sensitization of shaved mice in groups with or without drug i.p. on day 0, 1 of assay followed by ear-painting with DNFB on day 13 and measurements made of ear thickness before and 24, 48 & 72hr after ear painting. Histology of these thickened ears are consistent with accumulation of T cells and macrophages as seen with DTH. Results: Fluconazole enhanced DTH in mice at dosages of up to 6.0 mg total. Fluconazole dosages and time-points for sensitization as related to optimal DTH response was determined. Fluconazole was also found to reverse tolerization of mice to DNFB elicited by prior intravenous injection of DNBSO3 Kodak. Studies on vorconazole's effects on DTH response are in progress and seem to parallel much of our findings with fluconazole. Conclusions: Our findings suggest that patients receiving these imidazole drugs may not benefit just from their direct antifungal activity, but also benefit from the boost of their T cell and macrophage immune function. This work was supported in part by the Max Baer Heart Fund, Fraternal Order of Eagles (Granite City, IL).