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

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 It-1 beta concentration but not in other IL-1- or Th17-associated cytokines. It-1 beta 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, It-1 beta and airway NO production. (C) 2022 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.