Effects of recombinant human granulocyte-colony stimulating factor on neutropenic mice infected with Candida albicans: acceleration of recovery from neutropenia and potentiation of anti-C. albicans resistance

Abstract

The treatment of systemic candidal infection in neutropenic patients continues to be a major problem, and only 20% of patients survive despite treatment with amphotericin B (Amph B). Granulocyte colony-stimulating factor (G-CSF) is a haemopoietic glycoprotein that appears to control the survival, cycle, activation, proliferation and maturation of neutrophil granulocytes and promoter recovery from neutropenia. Confirming previous results, we observed that subcutaneous (s.c.) injection of recombinant human (rh) G-CSF in mice (30 micrograms kg-1 daily) increased the circulating leucocyte count (fourfold) on day 5 of treatment, and led to an expansion of the bone marrow myeloid compartment. The in vivo effect of rhG-CSF on murine resistance to systemic Candida albicans infection was also studied in neutropenic mice. Neutropenia was induced by intraperitoneal injection of a single dose of cyclophosphamide (CPA, 200 mg kg-1) 4 days before C. albicans infection and 2 days before rhG-CSF treatment. rhG-CSF administration showed a protective role on mice infected intravenously (i.v.) with one million C. albicans spores; all the untreated control mice died within 8 days after infection, whereas about 40% of mice treated with rhG-CSF remained alive for the same period. Furthermore, the survival rate was greater in host animals treated with combined Amph B and rhG-CSF than in those treated with Amph B alone. The number of C. albicans colony-forming units (CFU-C. albicans) in the kidney of infected mice was lower in the rhG-CSF-treated group than in the non-treated control mice. This suggests that the severity of infection is decreased in rhG-CSF-treated host animals.