PT  - JOURNAL ARTICLE
AU  - M. Brodlie
AU  - M.C. McKean
AU  - G.E. Johnson
AU  - A.E. Anderson
AU  - C.M.U. Hilkens
AU  - A.J. Fisher
AU  - P.A. Corris
AU  - J.L. Lordan
AU  - C. Ward
TI  - Raised interleukin-17 is immuno-localised to neutrophils in cystic fibrosis lung disease
AID  - 10.1183/09031936.00067110
DP  - 2010 Jan 01
TA  - European Respiratory Journal
PG  - erj00671-2010
4099  - http://erj.ersjournals.com/content/early/2010/11/25/09031936.00067110.short
4100  - http://erj.ersjournals.com/content/early/2010/11/25/09031936.00067110.full
AB  - 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.