Interleukin-1 beta is a potential mediator of airway nitric oxide deficiency in cystic fibrosis

Gyde Nissen; Elad Ben-Meir; Matthias Kopp; Michelle Shaw; Felix Ratjen; Hartmut Grasemann

doi:10.1016/j.jcf.2022.02.017

Interleukin-1 beta is a potential mediator of airway nitric oxide deficiency in cystic fibrosis

J Cyst Fibros. 2022 Jul;21(4):623-625. doi: 10.1016/j.jcf.2022.02.017. Epub 2022 Mar 5.

Authors

Gyde Nissen¹, Elad Ben-Meir², Matthias Kopp³, Michelle Shaw⁴, Felix Ratjen⁵, Hartmut Grasemann⁶

Affiliations

¹ Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada; Department of Pediatric Pneumology and Allergology, University of Lübeck, University Medical Center Schleswig-Holstein, Lübeck, Germany; Airway Research Center North (ARCN), Member of the German Center of Lung Research (DZL), Lübeck, Germany. Electronic address: gyde.nissen@uksh.de.
² Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada. Electronic address: elad.ben-meir@sickkids.ca.
³ Department of Pediatric Pneumology and Allergology, University of Lübeck, University Medical Center Schleswig-Holstein, Lübeck, Germany; Airway Research Center North (ARCN), Member of the German Center of Lung Research (DZL), Lübeck, Germany; Division of Pediatric Respiratory Medicine, Department of Pediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: matthias.kopp@insel.ch.
⁴ Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada; Translational Medicine, Research Institute, The Hospital for Sick Children and University of Toronto, Toronto, Canada. Electronic address: michelle.shaw@sickkids.ca.
⁵ Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada; Translational Medicine, Research Institute, The Hospital for Sick Children and University of Toronto, Toronto, Canada. Electronic address: felix.ratjen@sickkids.ca.
⁶ Division of Respiratory Medicine, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada; Translational Medicine, Research Institute, The Hospital for Sick Children and University of Toronto, Toronto, Canada. Electronic address: hartmut.grasemann@sickkids.ca.

PMID: 35260353
DOI: 10.1016/j.jcf.2022.02.017

Abstract

Airway nitric oxide (NO) deficiency is a hallmark of cystic fibrosis (CF), but the reasons for the reduced NO production in CF airways are unclear. Interleukin (IL)-1 pathway activation plays a role in early CF lung disease and is also involved in the regulation of NO synthase activity. Treatment of CF patients with the CFTR-targeting drug ivacaftor, among other beneficial effects, results in an increase in airway NO levels. In this longitudinal observational trial, we show that ivacaftor therapy leads to a significant reduction in sputum IL-1β concentration but not in other IL-1- or Th17-associated cytokines. IL-1β concentrations were closely linked to improvement in pulmonary function, measures of NO metabolism in sputum and exhaled NO. These data therefore suggest a potential interaction between transepithelial chloride conductance, IL-1β and airway NO production.

Keywords: Airway inflammation; Cystic fibrosis; Ivacaftor; Nitric oxide.

Publication types

Observational Study

MeSH terms

Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
Cystic Fibrosis* / complications
Cystic Fibrosis* / drug therapy
Cystic Fibrosis* / metabolism
Humans
Interleukin-1beta
Interleukin-8 / metabolism
Lung / metabolism
Nitric Oxide / metabolism

Substances

Interleukin-1beta
Interleukin-8
Cystic Fibrosis Transmembrane Conductance Regulator
Nitric Oxide