title: Low neonatal Toll-like receptor 4-mediated interleukin-10 production is associated with subsequent atopic dermatitis.
abstract: BACKGROUND
  Atopic dermatitis (AD) and respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are common diseases during early life. Impaired Th1-cell polarizing Toll-like receptor (TLR) responses play an important role in the pathogenesis of both diseases. Neonatal TLR-mediated production of Th1-type cytokines is decreased at birth, but rapidly increases during the first month of life.
  
  
  OBJECTIVE
  To determine whether decreased TLR-mediated production of Th1-polarizing cytokines, at the age of 1 month is associated with subsequent AD or RSV LRTI.
  
  
  METHODS
  A prospective healthy birth cohort study was performed. Whole blood concentrations of innate immune cells and TLR-mediated cytokine responses were measured at the age of 1 month in 291 neonates. AD was determined by a physician questionnaire at the age of 1 year and RSV LRTI was defined as parent-reported respiratory symptoms and presence of RSV RNA in a nose-throat specimen.
  
  
  RESULTS
  Of participating neonates, 45 (15%) developed AD and 41 (14%) developed RSV LRTI. Risks of AD and RSV LRTI were not associated (χ(2) , P = 1.00). AD was associated with decreased concentrations of basophils (7.6 vs. 14.0 × 10(6) /mL, P = 0.002) and plasmacytoid dendritic cells (17.0 vs. 20.5 × 10(6) /mL, P = 0.04), increased concentrations of NK-cells (79.7 vs. 45.1 × 10(6) /mL, P = 0.03), and twofold lower TLR4-mediated IL-10 production (P = 0.001). In contrast, RSV LRTI was associated neither with neonatal concentrations of innate immune cells, nor with TLR-mediated TNF-α, IL-12p70, IL-10 or IFN-α production.
  
  
  CONCLUSIONS
  Atopic dermatitis, but not RSV LRTI, is associated with distinct pre-symptomatic differences in the innate immune system. We hypothesize that decreased neonatal IL-10-mediated immune regulation during early life might play a causal role in the initiation of AD.
authors.affiliation: Department of Pediatrics, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Belderbos
authors.forename: E F
authors.initials: EF
authors.lastname: Knol
authors.forename: M L
authors.initials: ML
authors.lastname: Houben
authors.forename: G M
authors.initials: GM
authors.lastname: van Bleek
authors.forename: B
authors.initials: B
authors.lastname: Wilbrink
authors.forename: J L L
authors.initials: JL
authors.lastname: Kimpen
authors.forename: M
authors.initials: M
authors.lastname: Rovers
authors.forename: L
authors.initials: L
authors.lastname: Bont
mesh_terms: D001990:Bronchiolitis, Viral / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000503:physiopathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D016753:Interleukin-10