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 target-based therapy. We evaluated the role of doxycycline as a nonspecific inh...
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2011-01-01
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| Series: | Lung India |
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| Online Access: | http://www.lungindia.com/article.asp?issn=0970-2113;year=2011;volume=28;issue=3;spage=174;epage=179;aulast=Mishra |
| _version_ | 1828155693957382144 |
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| author | Amartya Mishra Parthasarathi Bhattacharya Sumit Paul Rantu Paul Snehasikta Swarnakar |
| author_facet | Amartya Mishra Parthasarathi Bhattacharya Sumit Paul Rantu Paul Snehasikta Swarnakar |
| author_sort | Amartya Mishra |
| collection | DOAJ |
| description | 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. |
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| format | Article |
| id | doaj.art-83d2c928c0c2404cadf0079238dcab62 |
| institution | Directory Open Access Journal |
| issn | 0970-2113 0974-598X |
| language | English |
| last_indexed | 2024-04-11T22:57:27Z |
| publishDate | 2011-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Lung India |
| spelling | doaj.art-83d2c928c0c2404cadf0079238dcab622022-12-22T03:58:20ZengWolters Kluwer Medknow PublicationsLung India0970-21130974-598X2011-01-0128317417910.4103/0970-2113.83972An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibitionAmartya MishraParthasarathi BhattacharyaSumit PaulRantu PaulSnehasikta SwarnakarBackground: 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.http://www.lungindia.com/article.asp?issn=0970-2113;year=2011;volume=28;issue=3;spage=174;epage=179;aulast=MishraBroncho alveolar lavage fluiddoxycyclineidiopathic pulmonary fibrosismatrix metalloproteinasevascular endothelial growth factor |
| spellingShingle | Amartya Mishra Parthasarathi Bhattacharya Sumit Paul Rantu Paul Snehasikta Swarnakar An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition Lung India Broncho alveolar lavage fluid doxycycline idiopathic pulmonary fibrosis matrix metalloproteinase vascular endothelial growth factor |
| title | An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition |
| title_full | An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition |
| title_fullStr | An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition |
| title_full_unstemmed | An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition |
| title_short | An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition |
| title_sort | alternative therapy for idiopathic pulmonary fibrosis by doxycycline through matrix metalloproteinase inhibition |
| topic | Broncho alveolar lavage fluid doxycycline idiopathic pulmonary fibrosis matrix metalloproteinase vascular endothelial growth factor |
| url | http://www.lungindia.com/article.asp?issn=0970-2113;year=2011;volume=28;issue=3;spage=174;epage=179;aulast=Mishra |
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