title: Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization.
abstract: BACKGROUND
  The role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known.
  
  
  OBJECTIVE
  To characterize the role of IL-26 in antibacterial host defense of human lungs.
  
  
  METHODS
  Intrabronchial exposure of healthy volunteers to endotoxin and vehicle was performed during bronchoscopy and bronchoalveolar lavage (BAL) samples were harvested. Intracellular IL-26 was detected using immunocytochemistry and immunocytofluorescence. This IL-26 was also detected using flow cytometry, as was its receptor complex. Cytokines and phosphorylated signal transducer and activator of transcription (STAT) 1 plus STAT3 were quantified using ELISA. Gene expression was analyzed by real-time polymerase chain reaction and neutrophil migration was assessed in vitro.
  
  
  RESULTS
  Extracellular IL-26 was detected in BAL samples without prior exposure in vivo and was markedly increased after endotoxin exposure. Alveolar macrophages displayed gene expression for, contained, and released IL-26. Th and cytotoxic T cells also contained IL-26. In the BAL samples, IL-26 concentrations and innate effector cells displayed a correlation. Recombinant IL-26 potentiated neutrophil chemotaxis induced by IL-8 and fMLP but decreased chemokinesis for neutrophils. Myeloperoxidase in conditioned media from neutrophils was decreased. The IL-26 receptor complex was detected in neutrophils and IL-26 decreased phosphorylated STAT3 in these cells. In BAL and bronchial epithelial cells, IL-26 increased gene expression of the IL-26 receptor complex and STAT1 plus STAT3. Finally, IL-26 increased the release of neutrophil-mobilizing cytokines in BAL but not in epithelial cells.
  
  
  CONCLUSIONS
  This study implies that alveolar macrophages produce IL-26, which stimulates receptors on neutrophils and focuses their mobilization toward bacteria and accumulated immune cells in human lungs.
authors.affiliation: 1 Unit for Lung and Airway Research, Institute of Environmental Medicine.
authors.forename: Karlhans F
authors.initials: KF
authors.lastname: Che
authors.forename: Sara
authors.initials: S
authors.lastname: Tengvall
authors.forename: Bettina
authors.initials: B
authors.lastname: Levänen
authors.forename: Elin
authors.initials: E
authors.lastname: Silverpil
authors.forename: Margaretha E
authors.initials: ME
authors.lastname: Smith
authors.forename: Muhammed
authors.initials: M
authors.lastname: Awad
authors.forename: Max
authors.initials: M
authors.lastname: Vikström
authors.forename: Lena
authors.initials: L
authors.lastname: Palmberg
authors.forename: Ingemar
authors.initials: I
authors.lastname: Qvarfordt
authors.forename: Magnus
authors.initials: M
authors.lastname: Sköld
authors.forename: Anders
authors.initials: A
authors.lastname: Lindén
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007113:Immunity, Innate; D007378:Interleukins / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*
chemical_list: C406767:IL26 protein, human; D007378:Interleukins
keywords: IL-10; T cell; infection; inflammation; macrophage