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

Summary. 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 promote recovery from neutropenia. Confirming previous results, we observed that subcutaneous (s.c.) injection of recombinant human (rh) G‐CSF in mice (30 μg 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. Zusammenfassung. Die Therapie der systemischen Candidose bei neutropenischen Patienten ist immer noch sehr problematisch; trotz Behandlung mit Amphotericin B überleben nur 20% der Patienten. Der Granulozytenkolonien stimulierende Faktor G‐CSF, ein hämatopoetisches Glykoprotein, scheint das Überleben, den Zyklus, die Proliferationsaktivierung und den Reifungsprozess der neutrophilen Granulozyten zu kontrollieren und die Normalisierung der Granulozytenzahl bei Neutropenie zu fördern. Die Beobachtung, daß die an Mäusen täglich durchgeführte. s.c. Injektion von rhG‐CSF (30 μg/kg) zu einer 4‐fachen Zunahme der zirkulierenden Leukozyten am 5. Tag der Behandlung und zu einer Proliferation der myeloischen Marksubstanz führte, bestätigte frühere Ergebnisse. Der in vivo Effekt von rhG‐***