Impaired phagocyte respiratory burst responses to opportunistic fungal pathogens in transplant recipients: in vitro effect of r‐metHuG‐CSF (Filgrastim)

Abstract

Phagocyte respiratory burst capacity in response to pathogenic fungi and the in vitro effects of granulocyte colony-stimulating factor (G-CSF) were examined in 15 normal volunteers and 39 transplant recipients (4 autologous and 4 allogeneic bone marrow, 3 heart, 10 liver, 8 lung, and 10 kidney). Chemiluminescence was measured for reaction mixtures of diluted whole blood, opsonized fungi, and luminol, with and without in vitro incubation with r-metHuG-CSF (Filgrastim). Transplant patients exhibited significantly impaired respiratory burst responses to conidia and yeast compared with controls, but this was reversed with Filgrastim. Responses to hyphae were low for both groups, and G-CSF had little or no effect. There was excellent correlation between responses to fungi and responses to opsonized zymosan. In vitro respiratory burst capacity is impaired in transplant recipients. This may predict susceptibility to invasive fungal infections. G-CSF can reverse impaired phagocyte function and is of potential benefit in the prevention and/or treatment of fungal infection in transplant patients.

Inhibition of Neutrophil Extracellular Trap Formation after Stem Cell Transplant by Prostaglandin E2

“…Neutrophils from autologous HSCT patients exhibit a diminished capacity to produce respiratory burst (6,9,10), whereas allogeneic HSCT patients exhibit defects in neutrophil chemotaxis in addition to impaired respiratory burst (6,11,12). However, the cause for neutrophil dysfunction has remained unclear.…”

Interferon-?? and Colony-Stimulating Factors as Adjuvant Therapy for Refractory Fungal Infections in Children

“…4 -10 Deficits in the respiratory burst of peripheral blood leukocytes from bone marrow and solid organ transplant patients exposed to fungi in vitro were reversed with G-CSF. 11 Administration of G-CSF to healthy human subjects increased the respiratory burst of PMNs after exposure to C. albicans, A. fumigatus and Rhizopus arrhizus and enhanced PMN-mediated killing of these fungi. 12,13 Among these mediators, IFN-␥ appears to have the broadest function.…”

Colony-Stimulating Factors in the Prevention and Management of Infectious Diseases

“…63,64 Similarly, perioperative G-CSF had no impact on postoperative infection rates in patients undergoing esophagectomy for esophageal cancer. 65 …”