In vivo effect of rhGM-CSF And rhG-CSF on monocyte HLA-DR expression of septic neonates.

Objective: To investigate the effect of rhGM-CSF and rhG-CSF on the monocyte HLA-DR expression of septic neonates.

Subjects: 60 septic neonates and 41 healthy ones. Septic neonates were randomly assigned into three treatment groups, the GM-CSF group [n=20, rhGM-CSF 5 mcg/kg/d for 4 days, intravenously over 2h (IV)], the G-CSF group (n=20, rhG-CSF 10 mcg/kg/d for 4 days, IV) and the placebo group (n=20, normal saline for 4 days, IV).

Measurements: Serial (days 0,1, 3 and 5 after the onset of sepsis) measurements of the percentage of HLA-DR positive monocytes (%HLA-DR+ monocytes) and mean fluorescence intensity (MFI) by flow-cytometry as well as the absolute monocyte counts (AMC).

Main Results: On day 0, the HLA-DR expression of the septic neonates (%HLA-DR+ monocytes: 38%+/-1.8% (mean+/-SEM) and MFI: 73+/-3.4) was significantly lower than the healthy control values (%HLA-DR+ monocytes: 68%+/-2% and MFI: 123+/-4.6) (P<0.0001, for both parameters). On follow up (days 1, 3 and 5), a significant increase of HLA-DR expression was observed in all the groups of septic neonates. Healthy control values of %HLA-DR+ monocytes were reached by day 1 in the GM-CSF group and by day 3 in the G-CSF and placebo groups. Healthy control values of MFI were reached by day 3 in all groups of septic neonates. The AMC showed a significant increase in the GM-CSF group (during the whole follow up period) and in the G-CSF group (for the first 3 days of follow up).

Conclusions: The monocyte HLA-DR expression is depressed on the onset of neonatal sepsis and is progressively restored during the following days. Treatment with rhGM-CSF results in an earlier increase of the number of monocytes expressing the HLA-DR.