Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection

Abstract Approaches to mitigate the severity of infections and of immune responses are still needed for the treatment of cystic fibrosis (CF) even with the success of highly effective modulator therapies. Previous studies identified reduced levels of melatonin in a CF mouse model related to circadia...

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Main Authors: Kristen R. Schaefer, Sara Rogers, Zachary Faber, Thomas J. Kelley
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-85948-6
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author Kristen R. Schaefer
Sara Rogers
Zachary Faber
Thomas J. Kelley
author_facet Kristen R. Schaefer
Sara Rogers
Zachary Faber
Thomas J. Kelley
author_sort Kristen R. Schaefer
collection DOAJ
description Abstract Approaches to mitigate the severity of infections and of immune responses are still needed for the treatment of cystic fibrosis (CF) even with the success of highly effective modulator therapies. Previous studies identified reduced levels of melatonin in a CF mouse model related to circadian rhythm dysregulation. Melatonin is known to have immunomodulatory properties and it was hypothesized that treatment with melatonin would improve responses to bacterial infection in CF mice. Data demonstrate that CF mice (G542X/G542X) treated with melatonin (10 µg/mL) in drinking water for 10 weeks had improved responses to airway infection with a clinical isolate of Pseudomonas aeruginosa. Melatonin-treated mice exhibited improved bacterial clearance, reduced inflammatory markers. Mice treated in drinking water for 1 week had improved bacterial clearance but no improvement in inflammation. Wild type (WT) control mice showed no response to melatonin treatment suggesting melatonin is eliciting a CF-specific response in this model. The efficacy of direct melatonin (1 µM) treatment to the airways was also tested and found to be ineffective. In conclusion, long-term systemic treatment with melatonin is an effective therapy in a CF mouse model that normalizes the response to airway infection to a WT pattern.
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spelling doaj-art-f64d265f0ff942a7bc576ce73e0d52812025-01-19T12:18:41ZengNature PortfolioScientific Reports2045-23222025-01-0115111210.1038/s41598-025-85948-6Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infectionKristen R. Schaefer0Sara Rogers1Zachary Faber2Thomas J. Kelley3Departments of Genetics and Genome Sciences, Case Western Reserve UniversityDepartments of Genetics and Genome Sciences, Case Western Reserve UniversityDepartments of Genetics and Genome Sciences, Case Western Reserve UniversityDepartments of Genetics and Genome Sciences, Case Western Reserve UniversityAbstract Approaches to mitigate the severity of infections and of immune responses are still needed for the treatment of cystic fibrosis (CF) even with the success of highly effective modulator therapies. Previous studies identified reduced levels of melatonin in a CF mouse model related to circadian rhythm dysregulation. Melatonin is known to have immunomodulatory properties and it was hypothesized that treatment with melatonin would improve responses to bacterial infection in CF mice. Data demonstrate that CF mice (G542X/G542X) treated with melatonin (10 µg/mL) in drinking water for 10 weeks had improved responses to airway infection with a clinical isolate of Pseudomonas aeruginosa. Melatonin-treated mice exhibited improved bacterial clearance, reduced inflammatory markers. Mice treated in drinking water for 1 week had improved bacterial clearance but no improvement in inflammation. Wild type (WT) control mice showed no response to melatonin treatment suggesting melatonin is eliciting a CF-specific response in this model. The efficacy of direct melatonin (1 µM) treatment to the airways was also tested and found to be ineffective. In conclusion, long-term systemic treatment with melatonin is an effective therapy in a CF mouse model that normalizes the response to airway infection to a WT pattern.https://doi.org/10.1038/s41598-025-85948-6
spellingShingle Kristen R. Schaefer
Sara Rogers
Zachary Faber
Thomas J. Kelley
Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection
Scientific Reports
title Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection
title_full Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection
title_fullStr Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection
title_full_unstemmed Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection
title_short Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection
title_sort efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection
url https://doi.org/10.1038/s41598-025-85948-6
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