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.
OBJECTIVE: To investigate the effect of human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) and fluconazole on anti-cryptococcal activity of monocytes from AIDSpatients 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 AIDSpatients was observed. GM-CSF treatment of monocytes from AIDSpatients 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.
Authors: Vivek Naranbhai; Christina C Chang; Raveshni Durgiah; Saleha Omarjee; Andrew Lim; Mahomed-Yunus S Moosa; Julian H Elliot; Thumbi Ndung'u; Sharon R Lewin; Martyn A French; William H Carr Journal: AIDS Date: 2014-03-13 Impact factor: 4.177
Authors: Lindsey B Rosen; Alexandra F Freeman; Lauren M Yang; Kamonwan Jutivorakool; Kenneth N Olivier; Nasikarn Angkasekwinai; Yupin Suputtamongkol; John E Bennett; Vasilios Pyrgos; Peter R Williamson; Li Ding; Steven M Holland; Sarah K Browne Journal: J Immunol Date: 2013-03-18 Impact factor: 5.422
Authors: David R Boulware; David B Meya; Tracy L Bergemann; Darin L Wiesner; Joshua Rhein; Abdu Musubire; Sarah J Lee; Andrew Kambugu; Edward N Janoff; Paul R Bohjanen Journal: PLoS Med Date: 2010-12-21 Impact factor: 11.069
Authors: Nancy F Crum-Cianflone; Pamela V Lam; Sarah Ross-Walker; Lindsey B Rosen; Steven M Holland Journal: Open Forum Infect Dis Date: 2017-10-05 Impact factor: 3.835