Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis
Idiopathic pulmonary fibrosis is a chronic, progressive, and lethal lung disease of unknown etiology. Antifibrotic drugs, including pirfenidone, are currently used for the treatment of the disease. The oral administration of pirfenidone is an effective therapy, as demonstrated by several clinical tr...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2020-11-01
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Series: | Frontiers in Pharmacology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.593620/full |
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Article |
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language |
English |
format |
Article |
sources |
DOAJ |
author |
Tomohito Okano Tetsu Kobayashi Taro Yasuma Taro Yasuma Corina N. D’Alessandro-Gabazza Masaaki Toda Hajime Fujimoto Hiroki Nakahara Yuko Okano Yuko Okano Atsuro Takeshita Atsuro Takeshita Kota Nishihama Haruko Saiki Atsushi Tomaru Valeria Fridman D’Alessandro Satoru Ishida Hiromi Sugimoto Yoshiyuki Takei Yoshiyuki Takei Esteban C. Gabazza Esteban C. Gabazza |
spellingShingle |
Tomohito Okano Tetsu Kobayashi Taro Yasuma Taro Yasuma Corina N. D’Alessandro-Gabazza Masaaki Toda Hajime Fujimoto Hiroki Nakahara Yuko Okano Yuko Okano Atsuro Takeshita Atsuro Takeshita Kota Nishihama Haruko Saiki Atsushi Tomaru Valeria Fridman D’Alessandro Satoru Ishida Hiromi Sugimoto Yoshiyuki Takei Yoshiyuki Takei Esteban C. Gabazza Esteban C. Gabazza Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis Frontiers in Pharmacology idiopathic pulmonary fibrosis pirfenidone intrapulmonary delivery oral therapy adverse effects drug delivery |
author_facet |
Tomohito Okano Tetsu Kobayashi Taro Yasuma Taro Yasuma Corina N. D’Alessandro-Gabazza Masaaki Toda Hajime Fujimoto Hiroki Nakahara Yuko Okano Yuko Okano Atsuro Takeshita Atsuro Takeshita Kota Nishihama Haruko Saiki Atsushi Tomaru Valeria Fridman D’Alessandro Satoru Ishida Hiromi Sugimoto Yoshiyuki Takei Yoshiyuki Takei Esteban C. Gabazza Esteban C. Gabazza |
author_sort |
Tomohito Okano |
title |
Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis |
title_short |
Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis |
title_full |
Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis |
title_fullStr |
Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis |
title_full_unstemmed |
Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis |
title_sort |
low-dose of intrapulmonary pirfenidone improves human transforming growth factorβ1-driven lung fibrosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2020-11-01 |
description |
Idiopathic pulmonary fibrosis is a chronic, progressive, and lethal lung disease of unknown etiology. Antifibrotic drugs, including pirfenidone, are currently used for the treatment of the disease. The oral administration of pirfenidone is an effective therapy, as demonstrated by several clinical trials, although it causes severe adverse events in some patients. We hypothesized that low-dose intrapulmonary delivery of pirfenidone is effective in human transforming growth factorβ1-driven pulmonary fibrosis. To demonstrate our hypothesis, we compared the therapeutic efficacy of varying doses of pirfenidone administered by oral and intranasal routes in a human transforming growth factor-β1 transgenic mouse with established pulmonary fibrosis. We found similar amelioration of lung cell infiltration, inflammatory and fibrotic cytokines, lung fibrosis score, and hydroxyproline content in mice with human transforming growth factor-β1-mediated pulmonary fibrosis treated with low-dose intranasal pirfenidone and high-dose oral pirfenidone. This study showed that pirfenidone is a potent inhibitor of human transforming growth factor-β1-driven lung fibrosis and that intrapulmonary delivery of low-dose pirfenidone produces therapeutic responses equivalent to high-dose of oral pirfenidone. |
topic |
idiopathic pulmonary fibrosis pirfenidone intrapulmonary delivery oral therapy adverse effects drug delivery |
url |
https://www.frontiersin.org/articles/10.3389/fphar.2020.593620/full |
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doaj-efcc9395978b4f508fef940bd7451fc32020-12-17T13:23:06ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-11-011110.3389/fphar.2020.593620593620Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung FibrosisTomohito Okano0Tetsu Kobayashi1Taro Yasuma2Taro Yasuma3Corina N. D’Alessandro-Gabazza4Masaaki Toda5Hajime Fujimoto6Hiroki Nakahara7Yuko Okano8Yuko Okano9Atsuro Takeshita10Atsuro Takeshita11Kota Nishihama12Haruko Saiki13Atsushi Tomaru14Valeria Fridman D’Alessandro15Satoru Ishida16Hiromi Sugimoto17Yoshiyuki Takei18Yoshiyuki Takei19Esteban C. Gabazza20Esteban C. Gabazza21Department of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Diabetes, Metabolism, and Endocrinology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Diabetes, Metabolism, and Endocrinology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Diabetes, Metabolism, and Endocrinology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Diabetes, Metabolism, and Endocrinology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanShionogi & Co, Ltd., Osaka, JapanShionogi & Co, Ltd., Osaka, JapanDepartment of Pulmonary and Critical Care Medicine, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Diabetes, Metabolism, and Endocrinology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanDepartment of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, JapanCenter for Intractable Diseases, Mie University Faculty and Graduate School of Medicine, Tsu, JapanIdiopathic pulmonary fibrosis is a chronic, progressive, and lethal lung disease of unknown etiology. Antifibrotic drugs, including pirfenidone, are currently used for the treatment of the disease. The oral administration of pirfenidone is an effective therapy, as demonstrated by several clinical trials, although it causes severe adverse events in some patients. We hypothesized that low-dose intrapulmonary delivery of pirfenidone is effective in human transforming growth factorβ1-driven pulmonary fibrosis. To demonstrate our hypothesis, we compared the therapeutic efficacy of varying doses of pirfenidone administered by oral and intranasal routes in a human transforming growth factor-β1 transgenic mouse with established pulmonary fibrosis. We found similar amelioration of lung cell infiltration, inflammatory and fibrotic cytokines, lung fibrosis score, and hydroxyproline content in mice with human transforming growth factor-β1-mediated pulmonary fibrosis treated with low-dose intranasal pirfenidone and high-dose oral pirfenidone. This study showed that pirfenidone is a potent inhibitor of human transforming growth factor-β1-driven lung fibrosis and that intrapulmonary delivery of low-dose pirfenidone produces therapeutic responses equivalent to high-dose of oral pirfenidone.https://www.frontiersin.org/articles/10.3389/fphar.2020.593620/fullidiopathic pulmonary fibrosispirfenidoneintrapulmonary deliveryoral therapyadverse effectsdrug delivery |