Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization

Am J Respir Crit Care Med. 2014 Nov 1;190(9):1022-31. doi: 10.1164/rccm.201404-0689OC.


Rationale: The role of the presumed Th17 cytokine IL-26 in antibacterial host defense of the lungs is not known.

Objectives: 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.

Measurements and main 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.

Keywords: IL-10; T cell; infection; inflammation; macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Cells, Cultured
  • Humans
  • Immunity, Innate*
  • Interleukins / physiology*
  • Lung / immunology*
  • Macrophages, Alveolar / physiology*
  • Neutrophils / physiology*


  • IL26 protein, human
  • Interleukins