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


METHODS
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.
Tascini
C
C
Department of Experimenta Medicine and Biochemical Sciences, University of Perugia, Italy.
Vecchiarelli
A
A
Preziosi
R
R
Francisci
D
D
Bistoni
F
F
Baldelli
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood*; D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003455:Cryptococcus neoformans / Q000187:drug effects*; D004357:Drug Synergism; D015725:Fluconazole / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D011994:Recombinant Proteins; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000935:Antifungal Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015725:Fluconazole