Anti-Inflammatory Influences of Cystic Fibrosis Transmembrane Conductance Regulator Drugs on Lung Inflammation in Cystic Fibrosis

• Published in: International journal of molecular sciences 2021-07, Vol.22 (14), p.7606
• Main Authors: Harwood, Kiera H, McQuade, Rachel M, Jarnicki, Andrew, Schneider-Futschik, Elena K
• Format: Article
• Language: English
• Subjects: Aminophenols - therapeutic use; Aminopyridines - therapeutic use; Anti-Inflammatory Agents - therapeutic use; Antimicrobial agents; Bacteria; Bacterial infections; Benzodioxoles - therapeutic use; Bronchopulmonary infection; CFTR modulator; Conductance; Cystic fibrosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis Transmembrane Conductance Regulator - drug effects; Cystic Fibrosis Transmembrane Conductance Regulator - metabolism; Cytokines; Drug development; Gene expression; Humans; Immune system; Indoles - therapeutic use; Inflammasomes; Inflammation; Inflammation - drug therapy; Inflammatory response; Interleukin 23; Ion Transport; ivacaftor; Leukocytes (neutrophilic); lumacaftor; Lung - metabolism; Lung - physiology; lung inflammation; Lungs; Macrophages - metabolism; Microorganisms; Mortality; Mutation; Neutrophils; Pathogens; Pneumonia - drug therapy; Quinolones - therapeutic use; Review; Signal Transduction; Staphylococcus infections; Therapeutic targets; Viscosity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22147606

Cystic fibrosis (CF) is caused by a defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR) which instigates a myriad of respiratory complications including increased vulnerability to lung infections and lung inflammation. The extensive influx of pro-inflammatory cells and production of mediators into the CF lung leading to lung tissue damage and increased susceptibility to microbial infections, creates a highly inflammatory environment. The CF inflammation is particularly driven by neutrophil infiltration, through the IL-23/17 pathway, and function, through NE, NETosis, and NLRP3-inflammasome formation. Better understanding of these pathways may uncover untapped therapeutic targets, potentially reducing disease burden experienced by CF patients. This review outlines the dysregulated lung inflammatory response in CF, explores the current understanding of CFTR modulators on lung inflammation, and provides context for their potential use as therapeutics for CF. Finally, we discuss the determinants that need to be taken into consideration to understand the exaggerated inflammatory response in the CF lung.