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1190 Activated Protein C Alters Neutrophil Reactive Oxygen Intermediates in Preterm Neonates
  1. HO Eliwan1,2,3,
  2. W Watson3,
  3. A O’Neill3,
  4. F O’Hare2,3,
  5. EJ Molloy1,3,4,5
  1. 1Neonatology, Our Lady’s Children’s Hospital
  2. 2Neonatology, National Maternity Hospital, Holles Street
  3. 3UCD School of Medicine and Medical Science, Conway Institute for Biomolecular and Biomedical Science, University College Dublin
  4. 4National Maternity Hospital, Holles Street
  5. 5Royal College of Surgeon, Dublin, Ireland

Abstract

Background Inflammation and infection are important aetiological factors in development of preterm birth. Inflammation is associated with many disorders of preterm infants including periventricular leukomalacia, chronic lung disease and necrotising eneterocolitis.

Aims To compare neutrophil and monocyte responses to lipopolysaccaride (LPS) +/-APC (activated protein c) stimulation in preterm neonates < 32 weeks gestation with adults controls.

Methods Whole blood was incubated with LPS +/-APC and Toll-like receptor4 (TLR4), CD11b expression, and reactive oxygen intermediate (ROI) release from neutophils and monocytes was examined by flow cytometry.

Results Both adults (n=15) and preterm neonates (n=30) had significantly increased LPS induced neutrophil CD11b expression but preterms are less responsive than adults. There was a significant increase in neutrophil ROI in response to LPS in adults and preterm neonates on day 1 and this was significantly reduced by APC There was significant higher baseline and endotoxin response of monocyte ROI in preterm neonates compared to adult (p<0.05). However APC had not reduced this response.

Conclusion Increased ROI release may mediate tissue damage and was significantly increased in preterm neonates and adults. APC reduced LPS-induced neutrophil ROI release. This may benefit preterm neonates at high risk of multiorgan inflammatory disorders but they are at high risk of haemorrhage. Further examination of APC mutants with anti-inflammatory but decreased anticoagulant properties is merited.

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