title: Early onset wheeze associated with enhanced combined IL-1β, IL-6, and IL-12/IL-23p40 in LPS-stimulated cord blood mononuclear cells.
abstract: BACKGROUND
  Neonates with a family history of atopy are at higher risk for developing wheezing in early life.
  
  
  OBJECTIVE
  From a birth cohort of at risk infants (first-degree family with atopic disease), we evaluated the influence of distinct intrinsic immunologic risk factors on wheezing disorders in the first 2 years of life.
  
  
  METHODS
  Cord blood samples were collected from 195 eligible subjects of a birth cohort of 253 subjects. The subjects studied were those who developed wheezing (n=34) or eczema (n=29) in the first 2 years of life, and 65 healthy control infants. At the time of thawing the viability of the cells were median 70% (range 67.5%-72.5%). Cytokines from lipopolysaccharide (LPS)-stimulated mononuclear cells were analysed using fluorescent-activated cell sorting-array and their profiles were evaluated using factor analysis.
  
  
  RESULTS
  Infants with wheeze were significantly associated with enhanced combined LPS stimulated IL-1β, IL-6, and IL-12/IL-23p40 compared with healthy controls (P=0.003). This profile was also associated with the increased risk for wheeze at 2 years of age (OR=2.45; 95% CI=1.50-3.93, P=0.001). LPS-stimulated cytokine IL-8 was also significantly higher in the wheeze group compared with healthy controls and eczema (P=0.003). Intracellular staining showed that monocytes are main producers of IL-6 and IL-8 from cord blood mononuclear cells. Most of the subjects were non-atopic with 3/34 (9%) wheeze and 9/29 (31%) eczema subjects sensitized to the common dietary or inhalant allergens.
  
  
  CONCLUSIONS
  In infants at genetic risk of atopy, wheeze but not eczema in the first 2 years of life is associated with intrinsic hyperresponsive innate cytokine responses which might predispose infants to wheeze development. Distinct pre-symptomatic hyperresponsive innate immune responses risk factors were found to be associated with early onset wheeze disorders, but not eczema.
authors.affiliation: Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: P L
authors.initials: PL
authors.lastname: Quah
authors.forename: I-C
authors.initials: IC
authors.lastname: Kuo
authors.forename: C H
authors.initials: CH
authors.lastname: Huang
authors.forename: L P-C
authors.initials: LP
authors.lastname: Shek
authors.forename: B W
authors.initials: BW
authors.lastname: Lee
authors.forename: K Y
authors.initials: KY
authors.lastname: Chua
mesh_terms: D017668:Age of Onset; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D004485:Eczema / Q000276:immunology; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018664:Interleukin-12 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D012135:Respiratory Sounds / Q000209:etiology* / Q000276:immunology*; D012307:Risk Factors
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018664:Interleukin-12