Related Experiment Video
Updated: Jan 26, 2026
Phage Therapy Application to Counteract Pseudomonas aeruginosa Infection in Cystic Fibrosis Zebrafish Embryos
Published on: May 12, 2020
Modulation of immune responses by elexacaftor/tezacaftor/ivacaftor therapy in cystic fibrosis: data from a
Francesca Lucca1, Anna Pianazzola1, Ilaria Meneghelli1
1Cystic Fibrosis Center, Azienda Ospedaliera Universitaria Integrata di Verona, P.le A. Stefani 1, Verona, 37126, Italy.
Background:
Elexacaftor-tezacaftor-ivacaftor (ETI) improves clinical outcomes in people with Cystic Fibrosis (pwCF), with possible anti-inflammatory properties. However, the molecular mechanisms underlying these effects remain unclear. This study investigates ETI's anti-inflammatory and immunomodulatory activity, focusing on essential signaling pathways.
Methods:
Forty-nine pwCF were followed for 24 months. PwCF underwent clinical and pulmonary function assessment along with sweat test chloride measurement. Blood samples were analyzed for red and white blood cell counts and C-reactive protein (CRP). Plasma cytokines were quantified and phospho-kinase arrays and western blotting were used to assess protein phosphorylation in peripheral blood mononuclear cells (PBMC) from pwCF and healthy controls, pre- and post-ETI. Gene expression was evaluated in patient-derived PBMC and CF bronchial epithelial cells in vitro.
Results:
ETI treatment significantly improved percent-predicted forced expiratory volume in 1 s (ppFEV1) and reduced intravenous antibiotic use. Inflammatory markers (including CRP) and circulating leukocytes decreased, especially lymphocytes and monocytes. Six of 27 pro-inflammatory cytokines were significantly downregulated. ETI strongly inhibited Signal Transducer and Activator of Transcription 5 (STAT5) phosphorylation in PBMC and CF epithelial cells, both in vivo and in vitro. This correlated with reduced interleukin IL-6, IL-8, and TNF-α mRNA levels. Pharmacological inhibition of JAK/STAT mimicked ETI effects on cytokine expression, supporting STAT5 as an important player involved in CF chronic inflammation.
Conclusion:
Long-term ETI treatment confirms clinical benefits and exerts measurable immunomodulatory effects, partially via inhibition of JAK/STAT signaling. These findings support its broader impact beyond CFTR correction. Further studies are warranted to explore long-term immunological outcomes, especially in younger patients initiating early therapy.
More Related Videos
06:14Optimized LC-MS/MS Method for the High-throughput Analysis of Clinical Samples of Ivacaftor, Its Major Metabolites, and Lumacaftor in Biological Fluids of Cystic Fibrosis Patients
Published on: October 15, 2017
07:04Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients
Published on: February 11, 2017
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:24Cystic Fibrosis: Management
Sinus disease and chronic...
01:36Humoral Immune Responses
01:40Cell-mediated Immune Responses
01:23Cells of the Adaptive Immune Response
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...