EFFECTS OF RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR ONNEUTROPENIC MICE INFECTED WITH CANDIDA-ALBICANS - ACCELERATION OF RECOVERY FROM NEUTROPENIA AND POTENTIATION OF ANTI-C-ALBICANS RESISTANCE

The treatment of systemic candidal infection in neutropenic patients c ontinues to be a major problem, and only 20% of patients survive despi te treatment with amphotericin B (Amph B). Granulocyte colony-stimulat ing factor (G-CSF) is a haemopoietic glycoprotein that appears to cont rol the survival, cycle, activation, proliferation and maturation of n eutrophil granulocytes and promote recovery from neutropenia. Confirmi ng previous results, we observed that subcutaneous (s.c.) injection of recombinant human (rh) G-CSF in mice (30 mu g 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 vi vo effect of rhG-CSF on murine resistance to systemic Candida albicans infection was also studied in neutropenic mice. Neutropenia was induc ed by intraperitoneal injection of a single dose of cyclophosphamide ( CPA, 200 mg kg(-1)) 4 days before C. albicans infection and 2 days bef ore rhG-CSF treatment. rhG-CSF administration showed a protective role on mice infected intravenously (i.v.) with one million C. albicans sp ores; all the untreated control mice died within 8 days after infectio n, whereas about 40% of mice treated with rhG-CSF remained alive for t he same period. Furthermore, the survival rate was greater in host ani mals treated with combined Amph B and rhG-CSF than in those treated wi th 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-tr eated group than in the non-treated control mice. This suggests that t he severity of infection is decreased in rhG-CSF-treated host animals.