The ability of recombinant human
granulocyte colony-stimulating factor (rhG-CSF) to protect and potentiate the activity of
antifungal agents against a lethal Trichosporon beigelii
infection in myelosuppressed mice was evaluated in this study. Mice were rendered neutropenic by 2 consecutive-day
intraperitoneal injections of
cyclophosphamide (200mg/kg). Recombinant hG-CSF, given subcutaneously at daily doses of 15, 60, and 120μg/kg for 6 days, shortened the period of
neutropenia and increased the number of circulating neutrophils in a dose-dependent manner. When rhG-CSF was administered to neutropenic mice before challenge with T. beigelii (5×106 CFU), it protected against the lethal
infection, resulting in improved survival and decreased numbers of fungal cells in the lung, liver, spleen and kidney. However, when the inoculum size increased to 7×106 CFU, a poorer result was obtained using a dose of 60μg/kg of rhG-CSF, suggesting that the activity of rhG-CSF is dependent on the severity of the T. beigelii
infection. Combined with
fluconazole (10 mg/kg) or
amphotericin B (1mg/kg), rhG-CSF improved the median survival time from 16 days with
fluconazole (59%) and 12 days with
amphotericin B (41%) alone to 20 days (93%) and 16 days (55%) in neutropenic mice treated with rhG-CSF plus
fluconazole or
amphotericin B, respectively. However, the combination of rhG-CSF and
itraconazole did not produce significant improvement in survival or clearance of fungal cells from the organs of neutropenic mice. These findings show that rhG-CSF may be a useful
immunomodulator against
Trichosporon infections in neutropenic mice and the therapeutic outcome improves when used in combination with
fluconazole or
amphotericin B.