title: Patterns of immune development in urban preschoolers with recurrent wheeze and/or atopy.
abstract: BACKGROUND
  Disadvantaged urban children have high rates of allergic diseases and wheezing, which are diseases associated with type 2-biased immunity.
  
  
  OBJECTIVE
  We sought to determine whether environmental exposures in early life influence cytokine responses that affect the development of recurrent wheezing illnesses and allergic sensitization.
  
  
  METHODS
  A birth cohort of 560 urban families was recruited from neighborhoods with high rates of poverty, and 467 (83%) children were followed until 3 years of age. Cytokine responses were measured in blood cell samples obtained at birth (cord blood) and ages 1 and 3 years. Cytokine responses were examined in relation to personal characteristics and environmental exposures to allergens and endotoxin and to the development of allergic sensitization and recurrent wheeze assessed at age 3 years.
  
  
  RESULTS
  Cytokine responses generally increased with age, but responses at birth were poorly predictive for those at ages 1 and 3 years. Exposure to certain allergens (cockroach, mouse, dust mite) was significantly associated with enhanced cytokine responses at age 3 years, including IFN-α and IL-10 responses to certain stimulants and responses to phytohemagglutinin. Regarding the clinical outcomes, reduced LPS-induced IL-10 responses at birth were associated with recurrent wheeze. In contrast, reduced respiratory syncytial virus-induced IL-8 responses and increased 5'-cytosine-phosphate-guanine-3' (CpG)-induced IL-12p40 and allergen-induced IL-4 responses were associated with atopy.
  
  
  CONCLUSIONS
  These findings suggest that diverse biologic exposures, including allergens and endotoxin, in urban homes stimulate the development of cytokine responses in early life, and that cytokine responses to specific microbial and viral stimuli are associated with the development of allergic sensitization and recurrent wheeze.
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, Wis. Electronic address: gern@medicine.wisc.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
authors.affiliation: Rho Inc, Chapel Hill, NC.
authors.forename: Agustin
authors.initials: A
authors.lastname: Calatroni
authors.affiliation: Rho Inc, Chapel Hill, NC.
authors.forename: Katy F
authors.initials: KF
authors.lastname: Jaffee
authors.affiliation: Rho Inc, Chapel Hill, NC.
authors.forename: Henry
authors.initials: H
authors.lastname: Lynn
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, Wis.
authors.forename: Amy
authors.initials: A
authors.lastname: Dresen
authors.affiliation: Boston University School of Medicine, Boston, Mass.
authors.forename: William W
authors.initials: WW
authors.lastname: Cruikshank
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Howard M
authors.initials: HM
authors.lastname: Lederman
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, NY.
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Sampson
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Mass.
authors.forename: Wayne
authors.initials: W
authors.lastname: Shreffler
authors.affiliation: Washington University School of Medicine and St Louis Children's Hospital, St Louis, Mo.
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Bacharier
authors.affiliation: National Institute of Allergy and Infectious Diseases, Bethesda, Md.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gergen
authors.affiliation: The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medicine School, Boston, Mass.
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
authors.affiliation: Columbia University Medical Center, New York, NY.
authors.forename: Meyer
authors.initials: M
authors.lastname: Kattan
authors.affiliation: Boston University School of Medicine, Boston, Mass.
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.affiliation: Boston University School of Medicine, Boston, Mass.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Sandel
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wood
authors.affiliation: Washington University School of Medicine and St Louis Children's Hospital, St Louis, Mo.
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bloomberg
mesh_terms: D000485:Allergens / Q000276:immunology; D002675:Child, Preschool; D002947:Cities / Q000453:epidemiology; D016207:Cytokines / Q000276:immunology; D004391:Dust / Q000032:analysis; D004731:Endotoxins / Q000276:immunology; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D005260:Female; D006798:Housing; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007223:Infant; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D016017:Odds Ratio; D012135:Respiratory Sounds / Q000276:immunology*; D012882:Skin Tests; D014481:United States / Q000453:epidemiology; D014505:Urban Population
chemical_list: D000485:Allergens; D016207:Cytokines; D004391:Dust; D004731:Endotoxins; D008070:Lipopolysaccharides; D007073:Immunoglobulin E
keywords: Cytokines; allergy; children; cord blood; immune development; mononuclear cells; wheezing