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Pirfenidone Mitigates Transforming Growth Factor-β-induced Inflammation after Viral Infection
Belinda J Thomas1,2,3,4, Keiko Kan-O1,2,3,5, Michael P Gantier2,3
1Monash Lung, Sleep, Allergy and Immunology, Monash University and Monash Medical Centre, Melbourne, Australia.
American Journal of Respiratory Cell and Molecular Biology
|April 16, 2025
Summary
Pirfenidone may offer a non-steroidal alternative for treating viral exacerbations in chronic obstructive pulmonary disease (COPD). This study shows pirfenidone effectively reduces influenza A virus infection and inflammation in COPD models, outperforming glucocorticosteroids.
Area of Science:
- Pulmonary Medicine
- Virology
- Immunology
Background:
- Chronic obstructive pulmonary disease (COPD) patients experience severe viral exacerbations due to blunted immune responses.
- Elevated transforming growth factor-beta (TGF-β) in COPD exacerbates lung inflammation and fibrosis during infections.
- Current glucocorticosteroid (GCS) treatments for COPD can worsen immunosuppression and infection risk.
Purpose of the Study:
- To investigate pirfenidone, an anti-fibrotic drug, as a potential non-steroidal treatment for viral exacerbations in COPD.
- To evaluate pirfenidone's efficacy in mitigating influenza A virus (IAV) infection and associated inflammation in COPD models.
Main Methods:
- Utilized murine models with lung-specific TGF-β overexpression or chronic cigarette smoke exposure combined with IAV infection.
- Administered pirfenidone orally or via inhalation, comparing it with GCS treatment.
- Assessed viral replication, inflammation, and immune responses in lung tissue and bronchoalveolar lavage fluid.
Main Results:
- TGF-β overexpression amplified IAV infection severity and airway inflammation by suppressing innate immune responses.
- Prophylactic pirfenidone administration curbed IAV infection and inflammation in both TGF-β and COPD models.
- Inhaled pirfenidone demonstrated superior inhibition of viral loads and inflammation compared to inhaled GCS.
Conclusions:
- Pirfenidone shows promise as a non-steroidal, preventative treatment for viral exacerbations in COPD.
- Inhaled pirfenidone may offer a safer alternative to GCS, mitigating viral damage without immunosuppression.
- Further investigation into pirfenidone, especially inhaled formulations, is warranted for COPD management.
