title: In vivo effect of recombinant human granulocyte colony-stimulating factor on phagocytic function and oxidative burst activity in septic neutropenic neonates.
abstract: Neutrophil dysfunction may contribute to an increased risk of sepsis in very-low-birth-weight (VLBW) neonates. The current study was designed to determine whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) affects absolute neutrophil count (ANC), phagocytic function, and oxidative burst in neutropenic VLBW neonates. Fourteen ventilated VLBW neonates were treated with rhG-CSF (10 microg/kg/day x 3 days i.v.). Phagocytic activity and oxidative burst were assessed before and after treatment with rhG-CSF using flow cytometry and fluorescence labeled opsonized Staphylococcus aureus. Control (nonseptic, nonneutropenic, n = 4), preeclamptic neutropenic (PET; nonseptic, n = 5), and septic neutropenic (n = 5) neonates with a gestational age ranging from 24 to 30 weeks were studied. In both PET and septic neonates, posttreatment phagocytosis more than doubled, but did not achieve matching control levels, whereas rhG-CSF treatment maintained the level of the phagocytic activity in the control group. The oxidative burst increased in all groups, but, again, PET and septic groups did not achieve matching control values. These effects occurred independent of a 2- to 12-fold increase in ANC. These results suggest that other disease-specific factors delay full functional recovery even after rhG-CSF treatment. We speculate that PET and septic neonates may remain susceptible to infection due to deficient neutrophil-killing capacity, even though their ANC returns to normal ranges. Augmenting immune function beyond the immediate period of ANC recovery suggests that prophylaxis with rhG-CSF may be an important risk reduction strategy for susceptible VLBW neonates.
authors.affiliation: Department of Pediatrics and Human Development, Michigan State University, East Lansing, Mich., USA.
authors.forename: Magdy
authors.initials: M
authors.lastname: Ahmad
authors.forename: Howard B
authors.initials: HB
authors.lastname: Fleit
authors.forename: Marc G
authors.initials: MG
authors.lastname: Golightly
authors.forename: Edmund F
authors.initials: EF
authors.lastname: La Gamma
mesh_terms: D005260:Female; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D005865:Gestational Age; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight / Q000276:immunology*; D015931:Intensive Care, Neonatal; D007958:Leukocyte Count; D009503:Neutropenia / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology*; D011225:Pre-Eclampsia / Q000276:immunology; D011247:Pregnancy; D011994:Recombinant Proteins; D016897:Respiratory Burst / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*
chemical_list: D005456:Fluorescent Dyes; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016650:Fluorescein-5-isothiocyanate