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カンオ ケイコ
KAN'O Keiko
神尾 敬子 所属 医学部 医学科（東京女子医科大学病院） 職種 助教 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読なし |
| 表題 | Pirfenidone Mitigates TGF-β-induced Inflammation Following Virus Infection. |
| 掲載誌名 | 正式名：American journal of respiratory cell and molecular biology 略 称：Am J Respir Cell Mol Biol ISSNコード：15354989/10441549 |
| 掲載区分 | 国外 |
| 巻・号・頁 | pp.Online |
| 著者・共著者 | Belinda J Thomas, Keiko Kan-O, Michael P Gantier, Ian Simpson, Julia G Chitty, Maggie Lam, Lovisa Dousha, Timothy A Gottschalk, Kate E Lawlor, Michelle D Tate, Saleela Ruwanpura, Huei Jiunn Seow, Kate L Loveland, Sheetal Deshpande, Xun Li, Kais Hamza, Paul T King, Jack A Elias, Ross Vlahos, Jane E Bourke, Philip G Bardin |
| 発行年月 | 2025/04 |
| 概要 | Infection by influenza A virus (IAV) and other viruses causes disease exacerbations in chronic obstructive pulmonary disease (COPD). Immune responses are blunted in COPD, a deficit compounded by current standard-of-care glucocorticosteroids (GCS) to further predispose patients to life-threatening infections. The immunosuppressive effects of elevated transforming growth factor-beta (TGF-β) in COPD may amplify lung inflammation during infections whilst advancing fibrosis. In the current study, we investigated potential repurposing of pirfenidone, currently used as an anti-fibrotic for idiopathic pulmonary fibrosis, as a non-steroidal treatment for viral exacerbations of COPD. Murine models of lung-specific TGF-β overexpression or chronic cigarette smoke exposure with IAV infection were used. Pirfenidone was administered daily by oral gavage commencing pre-or post-infection, while inhaled pirfenidone and GCS treatment pre-infection were also compared. Tissue and bronchoalveolar lavage were assessed for viral replication, inflammation and immune responses. Overexpression of TGF-β enhanced severity of IAV infection contributing to unrestrained airway inflammation. Mechanistically, TGF-β reduced innate immune responses to IAV by blunting interferon regulated gene (IRG) expression and suppressing production of anti-viral proteins. Prophylactic pirfenidone administration opposed these actions of TGF-β, curbing IAV infection and airway inflammation associated with TGF-β overexpression and cigarette smoke-induced COPD. Notably, inhaled pirfenidone caused greater inhibition of viral loads and inflammation than inhaled GCS. These proof-of-concept studies demonstrate that repurposing pirfenidone and employing a preventative strategy may yield substantial benefit over anti-inflammatory GCS in COPD. Pirfenidone can mitigate damaging virus exacerbations without attendant immunosuppressive actions and merits further investigation, particularly as an inhaled formulation. |
| DOI | 10.1165/rcmb.2024-0433OC |
| PMID | 40239009 |