title: Vitamin D enhances reactive oxygen intermediates production in phagocytic cells in term and preterm infants.
abstract: BACKGROUND
  Newborn infants are endotoxin tolerant which may be responsible for their increased susceptibility to bacterial sepsis. Vitamin D has an immunomodulatory effect and newborn infants are at risk of vitamin D deficiency. We examined the in vitro effect of 1, 25-dihydroxyvitamin D (1,25OHD) on whole blood phagocytic toll-like receptor 4 (TLR4), CD11b, and reactive oxygen intermediates (ROIs) in newborn infants during sepsis.
  
  
  METHODS
  Whole blood from preterm infants <32-wk gestation, control term neonates, and adults were sampled for phagocytic expression of ROI, TLR4, CD11b in response to lipopolysaccharide (LPS), and 1,25OHD using flow cytometer.
  
  
  RESULTS
  ROI production from newborn phagocytes incubated with LPS alone was decreased. Pretreatment with 1,25OHD demonstrated increased (P = 0.001) phagocytic ROI production in newborns but not in adults. 1,25OHD did not have any effect on TLR4 and CD11b in both newborns and adults. Pretreatment with ROI inhibitors (apocynin (APO) and diphenyleneiodonium), phosphoinositide 3-kinase (PI3K) inhibitor, and p38 inhibitor blocked neutrophil ROI production.
  
  
  CONCLUSIONS
  Neonatal phagocytic cells had diminished ROI production in the presence of LPS, however, pretreatment with 1,25OHD reversed this hyporesponsiveness. This action by 1,25OHD was mediated by activation of nicotinamide adenine dinucleotide phosphate oxidase system through PI3K signaling enzymes.
authors.affiliation: Department of Neonatology, National Maternity Hospital, Dublin, Ireland.|University College Dublin School of Medicine and Medical Science, Conway Institute for Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.|Department of Paediatrics, Children's University Hospital, Dublin, Ireland.
authors.forename: Chike
authors.initials: C
authors.lastname: Onwuneme
authors.affiliation: University College Dublin School of Medicine and Medical Science, Conway Institute for Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Blanco
authors.affiliation: University College Dublin School of Medicine and Medical Science, Conway Institute for Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
authors.forename: Amanda
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: University College Dublin School of Medicine and Medical Science, Conway Institute for Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland.
authors.forename: Bill
authors.initials: B
authors.lastname: Watson
authors.affiliation: Department of Neonatology, National Maternity Hospital, Dublin, Ireland.|Department of Paediatrics, Royal College of Surgeons, Dublin, Ireland.|Department of Neonatology, Our Lady's Children's Hospital, Dublin, Ireland.|Department of Paediatrics, Trinity College Dublin, National Children's Hospital, Dublin, Ireland.|Department of Neonatology, Coombe Women's and Infants University Hospital, Dublin, Ireland.
authors.forename: Eleanor J
authors.identifier: http://orcid.org/0000-0001-6798-2158
authors.initials: EJ
authors.lastname: Molloy
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000008:administration & dosage*; D016022:Case-Control Studies; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007231:Infant, Newborn; D007234:Infant, Premature; D009025:Morpholines / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D010587:Phagocytosis; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D002867:Chromones; D007093:Imidazoles; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011725:Pyridines; D017382:Reactive Oxygen Species; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D001205:Ascorbic Acid