title: Prenatal maternal stress and cord blood innate and adaptive cytokine responses in an inner-city cohort.
abstract: BACKGROUND
  Stress-elicited disruption of immunity begins in utero.
  
  
  OBJECTIVE
  Associations among prenatal maternal stress and cord blood mononuclear cell (CBMC) cytokine responses were prospectively examined in the Urban Environment and Childhood Asthma Study (n = 557 families).
  
  
  METHODS
  Prenatal maternal stress included financial hardship, difficult life circumstances, community violence, and neighborhood/block and housing conditions. Factor analysis produced latent variables representing three contexts: individual stressors and ecological-level strains (housing problems and neighborhood problems), which were combined to create a composite cumulative stress indicator. CBMCs were incubated with innate (lipopolysaccharide, polyinosinic-polycytidylic acid, cytosine-phosphate-guanine dinucleotides, peptidoglycan) and adaptive (tetanus, dust mite, cockroach) stimuli, respiratory syncytial virus, phytohemagglutinin, or medium alone. Cytokines were measured using multiplex ELISAs. Using linear regression, associations among increasing cumulative stress and cytokine responses were examined, adjusting for sociodemographic factors, parity, season of birth, maternal asthma and steroid use, and potential pathway variables (prenatal smoking, birth weight for gestational age).
  
  
  RESULTS
  Mothers were primarily minorities (Black [71%], Latino [19%]) with an income less than $15,000 (69%). Mothers with the highest cumulative stress were older and more likely to have asthma and deliver lower birth weight infants. Higher prenatal stress was related to increased IL-8 production after microbial (CpG, PIC, peptidoglycan) stimuli and increased tumor necrosis factor-alpha to microbial stimuli (CpG, PIC). In the adaptive panel, higher stress was associated with increased IL-13 after dust mite stimulation and reduced phytohemagglutinin-induced IFN-gamma.
  
  
  CONCLUSIONS
  Prenatal stress was associated with altered innate and adaptive immune responses in CBMCs. Stress-induced perinatal immunomodulation may impact the expression of allergic disease in these children.
authors.affiliation: The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. rerjw@channing.harvard.edu
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Wright
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Visness
authors.forename: Agustin
authors.initials: A
authors.lastname: Calatroni
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Grayson
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gold
authors.forename: Megan T
authors.initials: MT
authors.lastname: Sandel
authors.forename: Aviva
authors.initials: A
authors.lastname: Lee-Parritz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wood
authors.forename: Meyer
authors.initials: M
authors.lastname: Kattan
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Bloomberg
authors.forename: Melissa
authors.initials: M
authors.lastname: Burger
authors.forename: Alkis
authors.initials: A
authors.lastname: Togias
authors.forename: Frank R
authors.initials: FR
authors.lastname: Witter
authors.forename: Rhoda S
authors.initials: RS
authors.lastname: Sperling
authors.forename: Yoel
authors.initials: Y
authors.lastname: Sadovsky
authors.forename: James E
authors.initials: JE
authors.lastname: Gern
mesh_terms: D000293:Adolescent; D000328:Adult; D001741:Black or African American; D001249:Asthma / Q000097:blood* / Q000150:complications; D005260:Female; D005312:Fetal Blood / Q000276:immunology* / Q000378:metabolism; D006630:Hispanic or Latino; D006801:Humans; D007230:Infant, Low Birth Weight / Q000276:immunology; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D011203:Poverty; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D013312:Stress, Physiological / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014505:Urban Population; D055815:Young Adult
chemical_list: D018793:Interleukin-13; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma