An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition

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 targetbased 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.