title: Attenuated innate immune defenses in very premature neonates during the neonatal period.
abstract: BACKGROUND
  Antimicrobial responses have been shown to be profoundly attenuated in very preterm neonates when examined on cord blood. However, we lack data on these responses at the time these neonates are most vulnerable to infections.
  
  
  METHODS
  Multiple cytokine responses to two prototypic Toll-like receptor (TLR) agonists: lipopolysaccharide (LPS) (TLR4) and R848 (TLR7/8) were prospectively measured in preterm neonates born ≤30 wk of gestation (n = 50) during the first 28 d of age using whole blood and single-cell multiparameter flow cytometry assays. Results were compared to term neonates (n = 30) and adult controls (n = 25).
  
  
  RESULTS
  In preterm neonates, LPS and R848 responses remained attenuated in both cord blood and in the first 28 d of age. These responses showed significant maturation over time after adjusting for gestational age and were confirmed in monocytes and dendritic cells on a per-cell basis. We detected no major contribution of chorioamnionitis, maternal antenatal corticosteroids or magnesium sulfate treatment, labor, or mode of delivery to the maturation of cytokine responses.
  
  
  CONCLUSIONS
  Innate immune antimicrobial defenses are profoundly attenuated developmentally in very preterm neonates during the neonatal period, suggesting that exogenous factors drive the sustained systemic inflammation that has been linked to increased morbidities in these infants.
authors.affiliation: Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Marchant
authors.affiliation: Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Kan
authors.affiliation: Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Ashish A
authors.initials: AA
authors.lastname: Sharma
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.|Children's & Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Alice
authors.initials: A
authors.lastname: van Zanten
authors.affiliation: Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.|Children's & Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Kollmann
authors.affiliation: Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Rollin
authors.initials: R
authors.lastname: Brant
authors.affiliation: Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.|Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada.|Children's & Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Lavoie
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D005434:Flow Cytometry; D005865:Gestational Age; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007113:Immunity, Innate / Q000187:drug effects; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011446:Prospective Studies; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000097:blood / Q000276:immunology; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000097:blood / Q000276:immunology; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000097:blood / Q000276:immunology
chemical_list: D016207:Cytokines; D007093:Imidazoles; D008070:Lipopolysaccharides; C495345:TLR4 protein, human; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; C402365:resiquimod