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Antimicrobial Agents and Chemotherapy, January 2001, p. 96-104, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.96-104.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Effects of Cytokines and Fluconazole on the Activity of Human Monocytes against Candida albicans

A. L. Baltch,* R. P. Smith, M. A. Franke, W. J. Ritz, P. B. Michelsen, and L. H. Bopp

Stratton Veterans Affairs Medical Center and Albany Medical College, Albany, New York

Received 7 April 2000/Returned for modification 9 June 2000/Accepted 13 October 2000

This study evaluates the effects of cytokines, used singly and in combination, on the microbicidal activity of human monocyte-derived macrophages (MDM) against intracellular Candida albicans in the presence and absence of fluconazole. In the absence of fluconazole, the addition of tumor necrosis factor alpha (TNF-alpha ), interleukin-1beta (IL-1beta ), gamma interferon (IFN-gamma ), or IL-4 had no effect on the growth of C. albicans. In contrast, the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in decreased growth (P < 0.05), while the addition of IL-10 resulted in increased growth (P < 0.01). In the presence of fluconazole, only the addition of IFN-gamma resulted in an increase in the growth of C. albicans. In the presence or absence of fluconazole, all cytokine combinations except IFN-gamma plus GM-CSF caused significant decreases in growth (P < 0.01). IL-10 and IL-4 did not influence the activity of TNF-alpha or IL-1beta . In the absence or presence of C. albicans the addition of fluconazole, all of the cytokines studied, and combinations of fluconazole and selected cytokines caused increases in nitric oxide (NO) production (P < 0.01). Similar observations were made for superoxide (O2-) only in the presence of C. albicans. The greatest concentrations of NO and O2- were produced when C. albicans alone was present in the assays. Our results demonstrate that in the presence of low concentrations of fluconazole (0.1 times the MIC), selected cytokines and their combinations significantly increase the microbicidal activity of MDM against intracellular C. albicans.

* Corresponding author. Mailing address: Infectious Disease Research, Stratton VA Medical Center, Albany, NY 12208. Phone: (518) 462-3311, ext. 3080. Fax: (518) 462-3350. E-mail: BALTCH.ALDONA_{at}ALBANY.VA.GOV.

Antimicrobial Agents and Chemotherapy, January 2001, p. 96-104, Vol. 45, No. 1
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.1.96-104.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

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