title: Effect of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on polymorphonuclear neutrophils, monocytes or monocyte-derived macrophages combined with voriconazole against Cryptococcus neoformans.
abstract: The antifungal activity of voriconazole (VCZ) was tested against Cryptococcus neoformans (Cn) with and without the addition of polymorphonuclear neutrophils (PMN), monocytes or monocyte-derived macrophages (MDM) in vitro. Human effector cells with and without the addition of VCZ were incubated with Cn for 24 h. PMN, mono and MDM alone resulted in 61%, 34% and 23% inhibition of Cn, respectively (n = 3, P<0.01). VCZ at 0.01 and 0.05 microg ml(-1) alone resulted in 48% inhibition and 19% killing (n = 6). The addition of VCZ at 0.01 and 0.05 microg ml(-1) to human effector cells enhanced killing of Cn by 51% and 71% for the PMN, 41% and 58% for the mono, and 14% and 34% for the MDM, respectively. The addition of either granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) significantly enhanced the ability of human effector cells to kill Cn. G-CSF and GM-CSF plus PMN resulted in 47% and 46% killing, respectively; GM-CSF plus monocytes or MDM resulted in 31% or 22% killing, respectively. G-CSF and GM-CSF further enhanced the collaborative killing effect of human effector cells and VCZ. At 0.01 and 0.05 microg ml(-1) of VCZ, G-CSF or GM-CSF enhanced PMN killing to 92% and 93% or 87% and 94%, respectively. GM-CSF enhanced both mono and MDM with VCZ at 0.01 and 0.05 microg ml(-1) in killing Cn to 62% and 86%, and 61% and 84%, respectively. These results suggest that VCZ would have good efficacy in the treatment of Cn infection in humans. Furthermore, VCZ would have enhanced efficacy in clinical settings where either G-CSF or GM-CSF was being used.
authors.affiliation: Department of Medicine, Santa Clara Valley Medical Center, and California Institute for Medical Research, San Jose 95128, USA.
authors.forename: T
authors.initials: T
authors.lastname: Chiller
authors.forename: K
authors.initials: K
authors.lastname: Farrokhshad
authors.forename: E
authors.initials: E
authors.lastname: Brummer
authors.forename: D A
authors.initials: DA
authors.lastname: Stevens
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000276:immunology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology*; D011743:Pyrimidines / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D065819:Voriconazole