Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and ? 2 integrin expression Results of a randomized controlled trial

Abstract

The objective of this study was to investigate the effect of treatment with recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the neutrophil count and function of preterm neonates with documented sepsis. For this purpose 62 preterm neonates with proven sepsis and 19 healthy preterm ones were studied. Of the 62 patients, 27 septic neonates had an absolute neutrophil count (ANC) > 5000/mm3 (group A) and were scheduled not to receive rhG-CSF and 35/62 had an ANC < 5000/mm3 (n=35) and were randomly assigned either to receive rhG-CSF (group B) or not to receive it (group C). rhG-CSF (10 microg/kg) was administered for 3 consecutive days (0, 1, 2). The ANC, plasma levels of G-CSF (ELISA), neutrophil respiratory burst activity (NRBA) and neutrophil expression of CD11a, CD11b and CD11c (flow cytometry) were measured in all septic neonates on days 0 (onset of sepsis), 1, 3 and 5 and in the healthy neonates once within the first 2 days of life. We found that on day 0, G-CSF levels of all groups of septic neonates were significantly higher than those of the healthy ones. The highest levels were observed in group A. NRBA was diminished only in groups B and C and the expression of CD11a and CD11c was reduced in all groups of septic neonates. Administration of rhG-CSF resulted in a rapid and significant increase in ANC, NRBA and CD11a, CD11b and CD11c expression that persisted throughout the follow up. CONCLUSION; The administration of granulocyte colony stimulating factor to septic neonates significantly increases the absolute granulocyte count and enhances the neutrophil respiratory burst and beta2 integrin expression.

Effect of Granulocyte and Granulocyte Macrophage Colony Stimulating Factors (G-CSF and GM-CSF) on Neonatal Neutrophil Functions

“…Another finding of this study is the significant enhancement of superoxide release by priming neonatal and adult neutrophils with G-CSF and GM-CSF. This positive effect of CSF on the neutrophil superoxide release is in accordance with studies done in newborn infants in vivo (34,35) and in vitro (21,34). In contrast in adults, although the in vitro studies showed a consistent significant enhancement of fMLP-superoxide generation following G/GM-CSF priming (16,40,41,48,56,57), the in vivo superoxide production showed controversial results.…”

Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor Have Differential Effects on Neonatal and Adult Neutrophil Survival and Function

“…GM-CSF primes for PMAinduced respiratory burst to the same extent in term neonates, preterm neonates in intensive care, and adults in whole blood and to a greater degree than G-CSF in neonatal neutrophils (31). These in vitro effects of G-CSF and GM-CSF on neutrophil function studies have been confirmed in vivo in septic infants (32,33) and in children with cancer (34). In septic neutropenic preterm infants, although G-CSF increases neutrophil phagocytic capacity and oxidative capacity, levels do not reach those of normal preterm control infants (33).…”

A Randomized Case-Controlled Study of Recombinant Human Granulocyte Colony Stimulating Factor for the Treatment of Sepsis in Preterm Neutropenic Infants

“…21,24,26 However, in our study neutropenia recovered on 2.2 AE 1.4 days in Group I and rhG-CSF infusions were halted as soon as ANC rose above 1 Â 10 9 /L. Instead of administering rhG-CSF for constant periods, it may be more reasonable to perform daily CBC and terminate rhG-CSF infusions as soon as ANC is over 1 Â 10 9 /L.…”