An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition
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Published on: May 9, 2025
Amartya Mishra1, Parthasarathi Bhattacharya, Sumit Paul
1Department of Physiology, Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata, India.
Background:
Idiopatiic pulmonary fibrosis (IPF) is a disease of dysregulated fibrogenesis with abnormal matrix metalloproteinase (MMPs) activity, angiogenesis, and profibrotic milieu wherein MMPs inhibition appears to be target-based therapy. We evaluated the role of doxycycline as a nonspecific inhibitor of MMPs in IPF patients.
Materials And Methods:
Patients of IPF diagnosed on the basis of ATS-ERS consensus criteria were put on oral doxycycline in an open prospective trial. They were followed up for long term with spirometry, 6 min walk test (6MWT), St. Georges respiratory questionnaire (SGRQ), forced vital capacity (FVC), and repeat bronchoscopy while on doxycycline monotherapy for over 24 weeks. Both the initial and follow-up broncho alveolar lavage fluids (BALF) from IPF patients (n = 6) and control subjects (n = 6) were looked for MMP-9, -3, tissue inhibitor of metalloproteinase (TIMP)-1 and vascular endothelial growth factor (VEGF) expression. Additionally, doxycycline's action on MMP activities in vitro was tested in BALF of IPF patients.
Results:
Doxycycline intervention showed significant improvement in IPF patients in terms of change in 6MWT, SGRQ, FVC, and quality of life. The level of MMP-9, -3, TIMP-1 and VEGF in the BALF were found significantly higher in the IPF patients compared to the controls while doxycycline therapy reduced those parameters nearer to control value. Doxycycline also showed a significant dose-dependent reduction in the in vitro MMPs activities in BALF.
Conclusion:
Doxycycline shows significant prospect in the treatment of IPF through its anti MMPs activities. This is the first report on a case series of long-term doxycycline monotherapy in IPF patients.
Insights
Doxycycline, an inhibitor of matrix metalloproteinases (MMPs), improved idiopathic pulmonary fibrosis (IPF) symptoms and reduced key disease markers. This study highlights doxycycline
Area of Science:
- Pulmonary Medicine
- Fibrotic Diseases
- Pharmacology
Background:
- Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant fibrogenesis, matrix metalloproteinase (MMPs) activity, and angiogenesis.
- Targeting MMPs is a potential therapeutic strategy for IPF.
- Doxycycline's role as a nonspecific MMP inhibitor in IPF was investigated.
Purpose of the Study:
- To evaluate the efficacy of doxycycline monotherapy in patients with idiopathic pulmonary fibrosis.
- To assess the impact of doxycycline on MMP activity and related biomarkers in IPF.
Main Methods:
- An open prospective trial involving IPF patients treated with oral doxycycline for over 24 weeks.
- Long-term follow-up included spirometry, 6-minute walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ), and forced vital capacity (FVC).
- Bronchoalveolar lavage fluid (BALF) analysis for MMP-9, MMP-3, TIMP-1, and VEGF, with in vitro testing of doxycycline's effect on MMP activity.
Main Results:
- Doxycycline treatment led to significant improvements in 6MWT, SGRQ scores, FVC, and overall quality of life in IPF patients.
- IPF patients exhibited elevated levels of MMP-9, MMP-3, TIMP-1, and VEGF in BALF, which were reduced by doxycycline therapy.
- In vitro studies demonstrated a dose-dependent inhibition of MMP activity in BALF by doxycycline.
Conclusions:
- Doxycycline demonstrates significant therapeutic potential for IPF, primarily through its matrix metalloproteinase inhibitory actions.
- This study presents the first case series on long-term doxycycline monotherapy for idiopathic pulmonary fibrosis.
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