title: Enhanced T helper 1 and 2 cytokine responses at birth associate with lower risk of middle ear infections in infancy.
abstract: Respiratory tract infections and their symptoms are frequent during early childhood, but their risk factors, including the effect of early immune regulation, are less known. The aim of the study was to analyze whether stimulated cord blood cytokine production is associated with the frequency of respiratory tract infection symptoms or infections during the first year of life.
  
  
  
  The study population consisted of children of mothers from farm or non-farm rural environment from Austria, Finland, Germany, and Switzerland who participated in a prospective birth cohort study (PASTURE: Protection against Allergy-Study in Rural Environments) (N = 550). Cord blood samples were stimulated with the combination of phorbol ester and ionomycin (P/I) for 24 h, and the production of IL-5, IL-10, TNF-α, and IFN-γ was determined using ELISA. Information about infectious morbidity was collected using weekly diaries.
  
  
  
  P/I-stimulated production of IL-5 (adjusted risk ratio (aRR) for ≤median production, 0.37; 95% confidence interval (CI), 0.25-0.55, aRR for >median production, 0.41; 95% CI, 0.27-0.61 vs. production <detection limit) and IFN-γ (aRR for ≤median production, 0.62; 95% CI, 0.40-0.95, aRR for >median production, 0.39; 95% CI, 0.25-0.62 vs. production <detection limit) in cord blood were associated with lower number of weeks with reported middle ear infection. There was a tendency toward positive association with P/I-stimulated TNF-α production and middle ear infections.
  
  
  
  Our results suggest that increased Th2- and Th1-associated cytokine responses at birth may provide protection from later middle ear infections.
authors.affiliation: Department of Pediatrics, Central Hospital of Central Finland, Jyväskylä, Finland.|Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Bergroth
authors.affiliation: Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marjut
authors.initials: M
authors.lastname: Roponen
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Karvonen
authors.affiliation: Department of Obstetrics and Gynecology, Kuopio University Hospital, Kuopio, Finland.|Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
authors.forename: Leea
authors.initials: L
authors.lastname: Keski-Nisula
authors.affiliation: Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sami
authors.initials: S
authors.lastname: Remes
authors.affiliation: Children's Hospital Schwarzach, Schwarzach, Austria.
authors.forename: Josef
authors.initials: J
authors.lastname: Riedler
authors.affiliation: Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.|Children's Hospital, University of Zürich, Zürich, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Roduit
authors.affiliation: Department of Respiratory Disease, University of Besançon, UMR/CNRS 6249 Chrono-Environment, University Hospital, Besançon, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Dalphin
authors.affiliation: Department of Respiratory Disease, University of Besançon, UMR/CNRS 6249 Chrono-Environment, University Hospital, Besançon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Kaulek
authors.affiliation: Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
authors.forename: Georg J
authors.initials: GJ
authors.lastname: Loss
authors.affiliation: Christine Kühne Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.|Children's Hospital of Eastern Switzerland, St. Gallen, Switzerland.
authors.forename: Roger
authors.initials: R
authors.lastname: Lauener
authors.affiliation: Department of Environmental and Biological Sciences, University of Eastern Finland, Kuopio, Finland.
authors.forename: Maija-Riitta
authors.initials: MR
authors.lastname: Hirvonen
authors.affiliation: Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
authors.forename: Jon
authors.initials: J
authors.lastname: Genuneit
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Schmaußer-Hechfellner
authors.affiliation: Institute for Laboratory Medicine, Pathobiochemistry and Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.|Member of the German Center for Lung Research, UGMLC, Marburg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
authors.affiliation: Institute for Laboratory Medicine, Pathobiochemistry and Molecular Diagnostics, Philipps University of Marburg, Marburg, Germany.|Member of the German Center for Lung Research, UGMLC, Marburg, Germany.|Comprehensive Biomaterial Bank Marburg CBBM, Medical faculty, Philipps University of Marburg, Marburg, Germany.
authors.forename: Petra I
authors.initials: PI
authors.lastname: Pfefferle
authors.affiliation: Division of Experimental Asthma Research, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Member of the German Research Center for Lung Research, Borstel, Germany.|Institute for Experimental Medicine, Christian-Albrechts-Universitaet zu Kiel, Kiel, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krauss-Etschmann
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany.|Member of the German Center for Lung Research, CPC-M, Munich, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Schaub
authors.affiliation: Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany.|Member of the German Center for Lung Research, CPC-M, Munich, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: von Mutius
authors.affiliation: Department of Health Protection, National Institute for Health and Welfare, Kuopio, Finland.|Department of Public Health, University of Helsinki, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Pekkanen
mesh_terms: D002478:Cells, Cultured; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D004432:Ear, Middle / Q000276:immunology*; D005060:Europe / Q000453:epidemiology; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007223:Infant; D007231:Infant, Newborn; D015759:Ionomycin / Q000276:immunology; D011446:Prospective Studies; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000276:immunology*; D012424:Rural Population; D011795:Surveys and Questionnaires; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate
keywords: cord blood; cytokines; interferon-γ; interleukin-10; interleukin-5; middle ear infection; respiratory infections; respiratory symptoms; tumor necrosis factor-α