Persistent systemic monocyte and neutrophil activation in neonatal encephalopathy

Abstract

Aim: Circulating immune cell activation is associated with worse outcome in adult and animal models of brain injury. Our aim was to profile the systemic inflammatory response over the first week of life in infants at risk of neonatal encephalopathy and correlate early neutrophil and monocyte endotoxin and activation responses with outcome.

Methods: Prospective observational study in a tertiary referral university hospital including 22 infants requiring resuscitation at birth who had serial (five time points) neutrophil and monocyte CD11b (marker of cell adhesion) (intracellular Reactive oxygen intermediates) ROI (cell activation), and Toll-like receptor (endotoxin recognition) before and after endotoxin stimulation ex vivo compared to neonatal controls.

Results: All neonates requiring resuscitation at delivery (n = 122 samples) had higher neutrophil and monocyte CD11b and TLR-4 expressions compared with adults and neonatal controls. Neonates with abnormal neuroimaging and/or severe neonatal encephalopathy had increased CD11b, ROI and TLR-4. Increased PMN TLR-4 expression was associated with increased mortality in infants with neonatal encephalopathy (NE).

Conclusion: Innate immune dysregulation in the first week of life is associated with severity of outcome in neonatal brain injury in this cohort and may be amenable to immunomodulation.

Keywords:

• Brain injury
• CD11b
• immunity
• reactive oxygen intermediate
• Toll-like receptor 4

Acknowledgements

Authors thank Dr. John Murphy, Dr. Anne Twomey, Dr. Colm O’Donnell and Dr. Deirdre Sweetman for all their support and assistance in recruiting patients for this study. We wish to thank all the parents, babies, laboratory and hospital staff who generously participated in this project. In addition, we wish to thank Dr. Bryan Lynch for his expert Neurology opinion and Professor Billy Bourke for his support and encouragement.

Declaration of interest

Funded by the National Children’s Research Centre, Crumlin, Dublin 12, Ireland and the National Maternity Hospital Fund, Holles Street, Dublin 2, Ireland. The authors have no further disclosures or conflicts of interest