IN VIVO EFFECT OF rhG-CSF ON THE NUMBER AND FUNCTION OF NEONATAL NEUTROPHILS DURING SEPSIS. A RANDOMIZED CONTROLLED TRIAL. 56

Objective: To investigate the G-CSF levels in healthy and septic neonates and the effect of rhG-CSF administration on the absolute neutrophil count (ANC), respiratory burst activity (NRBA) and surface expression of adhesion molecules (b₂-intergrins) during neonatal sepsis.Subjects: 64 preterm neonates with proven sepsis and 19 healthy preterm neonates, matched for gestational age, were included in the study. The 27/64 septic neonates who had an ANC>5.000/mm³ did not receive rhG-CSF. The 37/64 who had an ANC<5.000/mm³ were randomly assigned either to receive rhG-CSF (n=19) or not to receive (n=18). Methods: rhG-CSF was administered subcutaneously at a dose of 10 μg/kg for 3 consecutive days. In the septic neonates, the ANC, NRBA, surface expression of CD11a/CD18, CD11c/CD18 and serum levels of G-CSF were serially measured before initiation of treatment (day 0) and at 3 subsequent time intervals (days 1, 3 and 5). In the healthy neonates, the same measurements were performed once, during the first 3 days of life. Results: 1) G-CSF levels of the septic neonates on day 0 were significantly higher than those of the healthy group. Furthermore, levels in neonates with an ANC>5,000/mm³ were higher than in neonates with ANC<5,000/mm³. Administration of rhG-CSF in the rhG-CSF-treated group resulted in a significant elevation of G-CSF levels that returned to baseline by day 5, 2) On follow-up a significant increase of ANC was observed in both groups of neonates with ANC<5,000/mm³, either treated or non-treated with rhG-CSF. The increase was more impressive in the G-CSF treated group. On the contrary, septic neonates with ANC>5,000 showed no significant change of ANC.3) The NRBA of septic neonates on day 0 was significantly lower that the NRBA of the healthy controls. A significant increase of NRBA between days 0 and 5 was observed only in the rhG-CSF-treated neonates. 4) On day 0, the percentage of neutrophils expressing the CD11a/CD18, and CD11c/CD18, but not the CD11b/CD18, was lower in the septic neonates compared to that found in the healthy control group. Serial measurements showed a significant increase in the expression of CD11a/CD18 and CD11c/CD18, but not of CD11b/CD18, in G-CSF-treated neonates and those with ANC>5.000/mm³. No significant change of the adhesion molecules was observed in neonates with ANC<5.000 who were not treated with rhG-CSF. Conclusions: Our results indicate the following: Administration of rhG-CSF in septic neonates with low ANC results in a significant increase of ANC, NRBA and neutrophil surface expression of the adhesion molecules CD11a/CD18 and CD11c/CD18. Administration of rhG-CSF may not be indicated in septic neonates with elevated ANC, who have succeeded in increasing the G-CSF production sufficiently enough to stimulate the number and partly the function of their neutrophils.