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

Lookup NU author(s): Dr Malcolm Brodlie, Dr Michael McKean, Dr Amy Anderson, Dr Catharien Hilkens, Professor Andrew Fisher, Professor Paul Corris, Dr James Lordan, Dr Christopher Ward

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Abstract

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


Publication metadata

Author(s): Brodlie M, McKean MC, Johnson GE, Anderson AE, Hilkens CM, Fisher AJ, Corris PA, Lordan JL, Ward C

Publication type: Article

Publication status: Published

Journal: European Respiratory Journal

Year: 2011

Volume: 37

Issue: 6

Pages: 1378-1385

Print publication date: 25/11/2010

ISSN (print): 0903-1936

ISSN (electronic): 1399-3003

Publisher: European Respiratory Society

URL: http://dx.doi.org/10.1183/09031936.00067110

DOI: 10.1183/09031936.00067110

PubMed id: 21109552


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