Interleukin-1 is associated with inflammation and structural lung disease in young children with cystic fibrosis

Samuel T Montgomery; A Susanne Dittrich; Luke W Garratt; Lidija Turkovic; Dario L Frey; Stephen M Stick; Marcus A Mall; Anthony Kicic; AREST CF

doi:10.1016/j.jcf.2018.05.006

Interleukin-1 is associated with inflammation and structural lung disease in young children with cystic fibrosis

J Cyst Fibros. 2018 Nov;17(6):715-722. doi: 10.1016/j.jcf.2018.05.006. Epub 2018 Jun 6.

Authors

Samuel T Montgomery¹, A Susanne Dittrich², Luke W Garratt³, Lidija Turkovic³, Dario L Frey², Stephen M Stick⁴, Marcus A Mall⁵, Anthony Kicic⁶; AREST CF⁷

Affiliations

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.
⁷ School of Paediatrics and Child Health, University of Western Australia, Nedlands 6009, Western Australia, Australia; Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth 6001, Western Australia, Australia; Murdoch Children's Research Institute, Parkville, 3052 Melbourne, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, 3052 Melbourne, Victoria, Australia.

PMID: 29884450
DOI: 10.1016/j.jcf.2018.05.006

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.

Keywords: Airway epithelium; Cystic fibrosis; Hypoxia; Interleukin (IL)-1; Mucus; Neutrophilic inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bronchoalveolar Lavage Fluid / immunology
Child, Preschool
Correlation of Data
Cystic Fibrosis* / immunology
Cystic Fibrosis* / pathology
Female
Humans
Inflammation / immunology*
Interleukin-1alpha / immunology*
Leukocyte Elastase / metabolism*
Lung* / diagnostic imaging
Lung* / pathology
Male
Neutrophils / enzymology
Tomography, X-Ray Computed / methods

Substances

Interleukin-1alpha
Leukocyte Elastase