J Pediatr Infect Dis 2017; 12(03): 176-183
DOI: 10.1055/s-0037-1603206
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Can Recombinant Granulocyte Colony Stimulating Factor Modulate Inflammatory Response in Extreme Low Gestational Age Newborns?: Effect of rhG-CSF on Cytokines in ELGAN

Prabhakar Kocherlokata
1   Department of Pediatrics, St Luke's Cornwall Hospital, Newburgh, New York, NY, United States
,
Mary Crow
2   Department of Medicine, Hospital for Special Surgery, New York, New York, NY, United States
,
Radhakrihna Vakkalanka
3   Genes, Cognition, and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, United States
,
Edmund F. La Gamma
4   Department of Pediatrics, Division of Newborn Medicine, The Regional Neonatal Center, Maria Fareri Children's Hospital at Westchester Medical Center, New York Medical College, Valhalla, New York, NY, United States
› Author Affiliations
Further Information

Publication History

08 December 2016

26 December 2016

Publication Date:
30 May 2017 (online)

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Abstract

Background Elevated levels of cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) are common in critically ill neonates, and may contribute to organ-based injury during acute illness contributing to neurodevelopmental delay. In both animals and human adults, recombinant human granulocyte-colony stimulating factor (rhG-CSF) is associated with a reduction in TNF-α blood levels.

Objective We aim to determine whether rhG-CSF treatment affects the blood levels of proinflammatory cytokines, TNF-α and IL-6 or the anti-inflammatory cytokine, IL-10 in extremely-low-gestational age neonates (ELGANs) compared with conventional medical management.

Methods The study included three groups of ELGANs between 2 and 4 days of age as subjects. Control group (n = 5); treated, nonseptic group (n = 10); and treated, septic group (n = 5) neonates were treated with conventional measures. In addition, the test subjects were treated with 10 μg/kg/d of rhG-CSF intravenously for 3 consecutive days. The levels of TNF-α, IL-6, and IL-10 were measured before and 24 hours after completion of the study.

Results The average TNF-α levels increased after birth in control subjects but did not rise in rhG-CSF treated subjects. A nonsignificant decrease of IL-6 and IL-10 blood levels was noted in all the subjects independent of the drug treatment.

Conclusion The use of rhG-CSF is associated with lower TNF-α levels in ELGANs.

Speculation During critical illness or sepsis, rhG-CSF may have unanticipated benefits as a drug that can elevate neutrophil number and function in neonates while simultaneously limiting collateral injury due to TNF-α.

Note

This work was presented in part at the Pediatric Academic Society Meeting in New Orleans, Louisiana, LA, United States by Kocherlakota, P; Vakkalanka, R; Crow MK; and La Gamma, EF: Effect of human granulocyte colony stimulating factor (rhG-CSF) on cytokines in VLBW neonates. Ped. Res. 44(4): A1044, 1998.


Contributors' Statement

Prabhakar Kocherlakota, MD contributed to the design, acquired data, performed the initial analysis, drafted the manuscript, and approved the final manuscript as submitted.


Mary Crow, MD supervised the analysis, reviewed the initial manuscript, and approved the final manuscript as submitted.


Edmund La Gamma, MD conceptualized and designed the study, designed the data collection instruments, drafted the initial manuscript, and approved the final manuscript as submitted.