Granulocyte Colony-Stimulating Factor Enhances the Phagocytic and Bactericidal Activity of Normal and Defective Human Neutrophils

Abstract

Granulocyte colony-stimulating factor (G-CSF) stimulates proliferation of myeloid cells and may be a valuable adjunct in prevention and treatment of neutropenia-associated infections. Neutrophil (PMNL) phagocytic and microbicidal functions against Staphylococcus aureus and Candida albicans blastoconidia were therefore evaluated. Bacterial phagocytosis and bactericidal activity were significantly enhanced by approximately 50%-70% after preincubation of normal PMNL with G-CSF in concentrations of 1000-4000 units/ml for 10 min at 37 degrees C. G-CSF in similar concentrations enhanced the defective bactericidal activity of PMNL from HIV-1-infected patients by approximately 70%-150% and reached the baseline control PMNL killing. However, G-CSF enhanced neither phagocytosis nor fungicidal activity of normal PMNL against C. albicans blastoconidia. These data demonstrate that G-CSF enhances the antibacterial but not the antifungal activities of human PMNL in vitro and also improves the defective PMNL bactericidal activity of HIV-1-infected patients.

Effects of recombinant granulocyte-colony stimulating factor administration duringMycobacterium aviuminfection in mice

“…In vitro studies have highlighted the priming effects of G-CSF on the antimicrobial activity of neutrophils [15,18,37,38]. In vivo experimental animal models have also described a protective effect of G-CSF administration [39±41].…”

“…On the other hand, neutrophil depletion in immunocompetent mice increased susceptibility to M. avium infection [12]. In patients with AIDS, neutrophil function is impaired [13±15] while neutropenia can be found associated with HIV infection, representing a risk for the development of infection [16,17] Recombinant human granulocyte-colony stimulating factor (rHuG-CSF) was shown to improve the neutrophil function defects in these patients, namely by improving their microbicidal activity [15,18]. Newman et al [19] have shown that neutrophils from AIDS patients significantly inhibited M. avium growth after administration of rHuG-CSF ex vivo.…”

Granulocyte colony-stimulating factor (G-CSF) transiently suppresses mitogen-stimulated T-cell proliferative response

“…It can also mobilize progenitor cells from the bone marrow into peripheral blood that can be used for hematopoietic reconstitution (Molineux et al, 1990;Bensinger et al, 1995;Schmitz et al, 1995). In addition to its role in the regulation of granulopoiesis, G-CSF enhances functions of mature neutrophils such as phagocytosis (Roilides et al, 1991), respiratory burst (Sullivan et al, 1993) and microbicidal activity (Vechiarelli et al, 1995). G-CSF has been shown to facilitate the clinical recovery of the nonneutropenic host in several animal models of infection (Dale et al, 1995) and in clinical trials of non-neutropenic patients with pneumonia (Welte et al, 1996).…”

Clostridium septicum Myonecrosis in Congenital Neutropenia

“…Rh-GCSF acts on granulocytopoietic progenitor cells to stimulate clonal proliferation of neutrophils, and it also improves neutrophil adhesion, chemotaxis, and phagocytic activity. [13][14][15] An international registry established to monitor the progress of patients who have SCN and are treated with rh-GCSF recently reported data collected on 853 patients. 1 The data show that 92.1% of patients respond to rh-GCSF at doses Ͻ30 g/kg per day.…”