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.
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