Samuel T Montgomery1, A Susanne Dittrich2, Luke W Garratt3, Lidija Turkovic3, Dario L Frey2, Stephen M Stick4, Marcus A Mall5, Anthony Kicic6. 1. School of Paediatrics and Child Health, University of Western Australia, Nedlands 6009, Western Australia, Australia. 2. Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL),University of Heidelberg, Heidelberg, Germany; Department of Pneumology and Critical Care Medicine, Thoraxklinik at the University Hospital Heidelberg, Heidelberg, Germany. 3. Telethon Kids Institute, University of Western Australia, Nedlands 6009, Western Australia, Australia. 4. School of Paediatrics and Child Health, University of Western Australia, Nedlands 6009, Western Australia, Australia; Telethon Kids Institute, University of Western Australia, Nedlands 6009, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth 6001, Western Australia, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands 6009,Western Australia, Australia. 5. Department of Translational Pulmonology, Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL),University of Heidelberg, Heidelberg, Germany; Department of Pediatric Pulmonology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany. 6. School of Paediatrics and Child Health, University of Western Australia, Nedlands 6009, Western Australia, Australia; Telethon Kids Institute, University of Western Australia, Nedlands 6009, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth 6001, Western Australia, Australia; Centre for Cell Therapy and Regenerative Medicine, School of Medicine and Pharmacology, University of Western Australia, Nedlands 6009,Western Australia, Australia; School of Public Health, Curtin University, Bentley 6102, Western Australia, Australia. Electronic address: Anthony.Kicic@telethonkids.org.au.
Abstract
BACKGROUND: Little is known about the role of interleukin (IL)-1 in the pathogenesis of cystic fibrosis (CF) lung disease. This study investigated the relationship between IL-1 signalling, neutrophilic inflammation and structural lung changes in children with CF. METHODS: Bronchoalveolar lavage fluid (BALf) from 102 children with CF were used to determine IL-1α, IL-1β, IL-8 levels and neutrophil elastase (NE) activity, which were then correlated to structural lung changes observed on chest computed tomography (CT) scans. RESULTS: IL-1α and IL-1β were detectable in BAL in absence of infection, increased in the presence of bacterial infection and correlated with IL-8 (p < 0.0001), neutrophils (p < 0.0001) and NE activity (p < 0.01 and p < 0.001). IL-1α had the strongest association with structural lung disease (p < 0.01) in the absence of infection (uninfected: p < 0.01 vs. infected: p = 0.122). CONCLUSION: Our data associates IL-1α with early structural lung damage in CF and suggests this pathway as a novel anti-inflammatory target.
BACKGROUND: Little is known about the role of interleukin (IL)-1 in the pathogenesis of cystic fibrosis (CF) lung disease. This study investigated the relationship between IL-1 signalling, neutrophilic inflammation and structural lung changes in children with CF. METHODS: Bronchoalveolar lavage fluid (BALf) from 102 children with CF were used to determine IL-1α, IL-1β, IL-8 levels and neutrophil elastase (NE) activity, which were then correlated to structural lung changes observed on chest computed tomography (CT) scans. RESULTS:IL-1α and IL-1β were detectable in BAL in absence of infection, increased in the presence of bacterial infection and correlated with IL-8 (p < 0.0001), neutrophils (p < 0.0001) and NE activity (p < 0.01 and p < 0.001). IL-1α had the strongest association with structural lung disease (p < 0.01) in the absence of infection (uninfected: p < 0.01 vs. infected: p = 0.122). CONCLUSION: Our data associates IL-1α with early structural lung damage in CF and suggests this pathway as a novel anti-inflammatory target.
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