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Updated: Feb 24, 2026
07:25
Visualization of Pseudomonas aeruginosa within the Sputum of Cystic Fibrosis Patients
Published on: July 16, 2020
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PDE4 Inhibitor Apremilast Rebalances Inflammatory Responses to Pseudomonas aeruginosa Infection in CF Rats
Linto Antony1,2, Lawrence Rasmussen1,2, Denise Stanford1,2
1Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Biorxiv : the Preprint Server for Biology
|February 23, 2026
Summary
Apremilast (Apr) shows promise in managing persistent airway inflammation in cystic fibrosis (CF) models. This phosphodiesterase 4 inhibitor rebalanced inflammation without increasing infection, suggesting it could complement CFTR modulator therapies.
Area of Science:
- Pulmonology
- Pharmacology
- Immunology
Background:
- Chronic airway inflammation persists in cystic fibrosis (CF) patients despite highly effective modulator therapy (HEMT).
- Existing anti-inflammatory treatments for CF are limited by side effects or incompatibility with CFTR modulators.
- Novel strategies are needed to rebalance inflammation without compromising host defense against infection.
Purpose of the Study:
- To evaluate the efficacy of apremilast (Apr), a selective phosphodiesterase 4 (PDE4) inhibitor, in modulating airway inflammation in a humanized CF (G551D) rat model.
- To assess the safety and compatibility of Apr with CFTR modulator therapy.
Main Methods:
- Humanized CF (G551D) rats were treated prophylactically with Apr and subsequently challenged with *Pseudomonas aeruginosa*.
- Lung function, lung injury, inflammatory markers (Th1/Th17 axes), bacterial burden, and CFTR expression/function were assessed.
- In vitro studies examined the effect of Apr on G551D-CFTR phosphorylation.
Main Results:
- Short-term prophylactic Apr treatment preserved lung function and reduced lung injury in CF rats.
- Apr broadly modulated inflammatory responses, particularly Th1 and Th17 pathways.
- Apr did not significantly increase bacterial burden or negatively impact CFTR expression.
- Apr enhanced G551D-CFTR phosphorylation in vitro, indicating compatibility with HEMT.
Conclusions:
- Apremilast demonstrates potential as an adjunct therapy to CFTR modulators for managing airway inflammation in CF.
- Apr may help rebalance inflammation in CF without compromising host defense mechanisms.
- Further investigation into Apr's role in CF treatment is warranted.
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