title: Persistent systemic monocyte and neutrophil activation in neonatal encephalopathy.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Paediatrics , National Maternity Hospital , Dublin , Ireland .|b UCD School of Medicine & Medical Sciences, Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin , Dublin , Ireland .|c National Children's Research Centre , Crumlin , Dublin , Ireland .
authors.forename: F M
authors.initials: FM
authors.lastname: O'Hare
authors.affiliation: b UCD School of Medicine & Medical Sciences, Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin , Dublin , Ireland .
authors.forename: R W G
authors.initials: RW
authors.lastname: Watson
authors.affiliation: b UCD School of Medicine & Medical Sciences, Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin , Dublin , Ireland .
authors.forename: A
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: b UCD School of Medicine & Medical Sciences, Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin , Dublin , Ireland .
authors.forename: A
authors.initials: A
authors.lastname: Blanco
authors.affiliation: a Department of Paediatrics , National Maternity Hospital , Dublin , Ireland .|d Department of Radiology , Children's University Hospital , Dublin , Ireland .
authors.forename: V
authors.initials: V
authors.lastname: Donoghue
authors.affiliation: a Department of Paediatrics , National Maternity Hospital , Dublin , Ireland .|b UCD School of Medicine & Medical Sciences, Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin , Dublin , Ireland .|e Department of Paediatrics , Royal College of Surgeons in Ireland , Dublin , Ireland .|f Department of Neonatology , Our Lady's Children's Hospital , Crumlin , Dublin , Ireland .|g Department of Paediatrics , Trinity College Dublin , Dublin , Ireland , and.|h Academic Paediatric Centre, National Children's Hospital , Tallaght , Dublin , Ireland.
authors.forename: E J
authors.initials: EJ
authors.lastname: Molloy
mesh_terms: D000328:Adult; D001930:Brain Injuries / Q000378:metabolism*; D039481:CD11b Antigen / Q000378:metabolism; D016022:Case-Control Studies; D036861:Delivery, Obstetric; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000378:metabolism; D012151:Resuscitation; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D017382:Reactive Oxygen Species; D051197:Toll-Like Receptor 4
keywords: Brain injury; CD11b; Toll-like receptor 4; immunity; reactive oxygen intermediate