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Low-Dose of Intrapulmonary Pirfenidone Improves Human Transforming Growth Factorβ1-Driven Lung Fibrosis

Okano Tomohito 三重大学

2021.06.29

概要

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 factorβ1 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 factorβ1-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 factorβ1-driven lung fibrosis and that intrapulmonary delivery of low-dose pirfenidone produces therapeutic responses equivalent to high-dose of oral pirfenidone.

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Frontiers in Pharmacology | www.frontiersin.org

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Okano et al.

Intrapulmonary Pirfenidone for Pulmonary Fibrosis

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The remaining authors declare that the research was conducted in the absence of

any commercial or financial relationships that could be construed as a potential

conflict of interest.

Copyright © 2020 Okano, Kobayashi, Yasuma, D’alessandro-Gabazza, Toda,

Fujimoto, Nakahara, Okano, Takeshita, Nishihama, Tomaru, Fridman

D’alessandro, Ishida, Sugimoto, Takei and Gabazza. This is an open-access

article distributed under the terms of the Creative Commons Attribution License

(CC BY). The use, distribution or reproduction in other forums is permitted,

provided the original author(s) and the copyright owner(s) are credited and that

the original publication in this journal is cited, in accordance with accepted academic

practice. No use, distribution or reproduction is permitted which does not comply

with these terms.

Conflict of Interest: ECG, CND-G, and TY have received a grant from Shionogi

Co. to support in part the execution of the experimental study reported in the

Frontiers in Pharmacology | www.frontiersin.org

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November 2020 | Volume 11 | Article 593620

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