Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease

Eur Respir J. 2011 Jun;37(6):1378-85. doi: 10.1183/09031936.00067110. Epub 2010 Nov 25.

Abstract

Interleukin (IL)-17 is pivotal in orchestrating the activity of neutrophils. Neutrophilic inflammation is the dominant pathology in cystic fibrosis (CF) lung disease. We investigated IL-17 protein expression in the lower airway in CF, its cellular immunolocalisation and the effects of IL-17 on CF primary bronchial epithelial cells. Immunohistochemistry was performed on explanted CF lungs and compared with the non-suppurative condition pulmonary hypertension (PH). Airway lavages and epithelial cultures were generated from explanted CF lungs. Immunoreactivity for IL-17 was significantly increased in the lower airway epithelium in CF (median 14.1%) compared with PH (2.95%, p=0.0001). The number of cells staining positive for IL-17 in the lower airway mucosa was also increased (64 cells·mm(-1) compared with 9 cells·mm(-1) basement membrane, p=0.0005) and included both neutrophils in addition to mononuclear cells. IL-17 was detectable in airway lavages from explanted CF lungs. Treatment of epithelial cultures with IL-17 increased production of IL-8, IL-6 and granulocyte macrophage colony-stimulating factor. In conclusion, immunoreactive IL-17 is raised in the lower airway of people with CF and localises to both neutrophils and mononuclear cells. IL-17 increases production of pro-neutrophilic mediators by CF epithelial cells, suggesting potential for a positive feedback element in airway inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis / microbiology
  • Cystic Fibrosis / pathology
  • Granulocyte-Macrophage Colony-Stimulating Factor / biosynthesis
  • Humans
  • Interleukin-17 / immunology*
  • Interleukin-6 / biosynthesis
  • Interleukin-8 / biosynthesis
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Lung Transplantation
  • Neutrophils / immunology*
  • Pneumonia, Bacterial / immunology*
  • Pneumonia, Bacterial / microbiology
  • Sputum / microbiology

Substances

  • Interleukin-17
  • Interleukin-6
  • Interleukin-8
  • Granulocyte-Macrophage Colony-Stimulating Factor