Granulocyte-macrophage colony-stimulating factor and fluconazole enhance anti-cryptococcal activity of monocytes from AIDS patients.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Granulocyte-macrophage colony-stimulating factor and fluconazole enhance anti-cryptococcal activity of monocytes from AIDS patients.

AIDS. 1999 Jan 14;13(1):49-55. Unique Identifier : AIDSLINE MED/99223951
Tascini C; Vecchiarelli A; Preziosi R; Francisci D; Bistoni F; Baldelli F; Department of Experimenta Medicine and Biochemical Sciences,; University of Perugia, Italy.

Abstract: OBJECTIVE: To investigate the effect of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) and fluconazole on anti-cryptococcal activity of monocytes from AIDS patients and normal subjects. DESIGN: The effect of GM-CSF and fluconazole on fungistatic and fungicidal activity of monocytes was studied in an in vitro system. METHODS: Monocytes were treated in vitro with hrGM-CSF and fluconazole or either agent alone for 24 or 48 h, and fungistatic and fungicidal activity was evaluated in a colony-forming unit inhibition assay. CD11b/CD18 expression in monocytes was measured by flow cytometry analysis. Superoxide anion generation by peripheral blood monocytes was measured in the presence of pre-opsonized zymosan. RESULTS: Defective antifungal capacity of monocytes from AIDS patients was observed. GM-CSF treatment of monocytes from AIDS patients increased fungistatic activity, and the combination of hrGM-CSF and fluconazole resulted in fungicidal activity. The mechanisms involved in the GM-CSF-mediated effect appeared to be mediated by (i) enhancement of phagocytic activity, (ii) increase of superoxide anion generation, and (iii) upregulation of CD11b/CD18 expression on the monocyte surface. CONCLUSIONS: Our data highlight the effect of GM-CSF on anti-cryptococcal activity of human monocytes and show a synergistic effect of GM-CSF with fluconazole, suggesting a new therapeutic strategy in the treatment of cryptococcosis.

Keywords: JOURNAL ARTICLE Acquired Immunodeficiency Syndrome/*BLOOD Adult Antifungal Agents/*PHARMACOLOGY Cells, Cultured Cryptococcus neoformans/*DRUG EFFECTS Drug Synergism Fluconazole/*PHARMACOLOGY Granulocyte Macrophage Colony-Stimulating Factors, Recombinant/ *PHARMACOLOGY Human Monocytes/*DRUG EFFECTS/IMMUNOLOGY/MICROBIOLOGY Superoxides/METABOLISM Tumor Necrosis Factor/METABOLISM
990930
A9991342

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