title: Mediators of neutrophil function in children with protracted bacterial bronchitis.
abstract: BACKGROUND
  Protracted bacterial bronchitis (PBB) is a common and treatable cause of chronic wet cough in children in which the mechanisms are not understood. This study investigates the IL-1 pathway and a neutrophil gene expression signature in PBB.
  
  
  METHODS
  BAL was collected from children in an experimental cohort (n = 21, PBB; n = 33, control subjects), and a second validation cohort (n = 36, PBB; n = 11, control subjects). IL-1β, IL-1 receptor antagonist (IL-1RA), and α-defensins 1-3 were assayed by enzyme-linked immunosorbent assay, western blot, and quantitative real-time polymerase chain reaction, together with selected IL-1 pathway members and neutrophil-related molecules.
  
  
  RESULTS
  In the experimental cohort, children with symptomatic PBB had significantly higher levels of IL-1β and α-defensin gene and protein expression. Expression of the neutrophil chemokine receptor C-X-C motif receptor 2 was also higher in PBB. IL-1RA protein was higher, however, the IL-1RA:IL-1β ratio was lower in children with PBB than control subjects. In the validation cohort, protein and gene expression of IL-1β and α-defensins 1-3 were confirmed higher, as was gene expression of IL-1 pathway members and C-X-C motif receptor 2. IL-1β and α-defensin 1-3 levels lowered when PBB was treated and resolved. In children with recurrent PBB, gene expression of the IL-1β signaling molecules pellino-1 and IL-1 receptor-associated kinase 2 was significantly higher. IL-1β protein levels correlated with BAL neutrophilia and the duration and severity of cough symptoms. IL-1β and α-defensin 1-3 levels were highly correlated.
  
  
  CONCLUSIONS
  PBB is characterized by increased IL-1β pathway activation. IL-1β and related mediators were associated with BAL neutrophils, cough symptoms, and disease recurrence, providing insight into PBB pathogenesis.
authors.affiliation: The Priority Research Centre for Asthma and Respiratory Diseases, Callaghan, NSW; The University of Newcastle, Callaghan, NSW. Electronic address: katherine.baines@newcastle.edu.au.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Baines
authors.affiliation: Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW.
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
authors.affiliation: Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW; Hunter Medical Research Institute, John Hunter Hospital, New Lambton Heights, NSW.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Yerkovich
authors.affiliation: School of Medicine, The University of Queensland, Brisbane, QLD; Qld Lung Transplant Service, The Prince Charles Hospital, Brisbane, QLD; Department of Respiratory Medicine, Queensland Children's Medical Research Institute, Royal Children's Hospital, Brisbane, QLD; Child Health Division, Menzies School of Health Research, Darwin, NT, Australia.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Chang
authors.affiliation: Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW; School of Medicine, The University of Queensland, Brisbane, QLD.
authors.forename: Julie M
authors.initials: JM
authors.lastname: Marchant
authors.affiliation: Department of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, NSW.
authors.forename: Melanie
authors.initials: M
authors.lastname: Carroll
authors.affiliation: The Priority Research Centre for Asthma and Respiratory Diseases, Callaghan, NSW; The University of Newcastle, Callaghan, NSW.
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Simpson
authors.affiliation: The Priority Research Centre for Asthma and Respiratory Diseases, Callaghan, NSW; The University of Newcastle, Callaghan, NSW.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Gibson
mesh_terms: D001424:Bacterial Infections / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001991:Bronchitis / Q000235:genetics / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D023084:alpha-Defensins / Q000235:genetics / Q000378:metabolism*
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D053583:Interleukin-1beta; D023084:alpha-Defensins