BACKGROUND: Interleukin-8 ( IL-8)-dependent neutrophilia is a feature of innate immunity to lung microbial pathogens, yet many lung diseases themselves encompass pathologic consequences of chronic, excessive, IL-8 release. These diseases include cystic fibrosis, COPD, idiopathic pulmonary fibrosis, bronchiectasis, sarcoidosis and ARDS.
AIM: We set out to generate a new transgenic model for lung hyper-expression of IL-8 to dissect the consequences of IL-8 lung expression for host immunity and pathogenesis.
METHODS: We generated a new transgenic line that expresses high levels of IL-8 in the lung through targeting human IL-8 cDNA on a Clara-cell 10 (CC10) lung bronchial epithelial promoter. We studied the effects of expression on susceptibility to Pseudomonas and Aspergillus infection and to chronic lung pathology. Changes were analysed at the level of cellular populations, transcriptomic and histopathologic changes.
RESULTS: IL-8 transgenics showed enhanced protection to lung challenge with Pseudomonas or Aspergillus, associated with enhanced neutrophil function and with up-regulation of additional innate and adaptive pathways. However, this came with evidence of mucus hypersecretion, remodelling and impaired lung function.
CONCLUSIONS: This study provides new insights into the specific pathways involved in lung damage by chronic IL-8 secretion. Host protection comes at a high cost of lung remodelling and impaired function.
Full conference title:
- ERS 26th (2016)