Basic study on the drug repositioning of PDE4 inhibitors for interstitial pneumonia in the lung

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11071
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: The University of Tokyo
• Principal Investigator: Hirose kayo 東京大学, 医学部附属病院, 病院診療員 (40532221)
• Co-Investigator(Kenkyū-buntansha): 山田 芳嗣 東京大学, 医学部附属病院, 教授 (30166748)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: フォスフォジエステラーゼ４ / 間質性肺炎 / ドラッグリポジショニング

Outline of Final Research Achievements

The applicants explored the possibility that PDE4 expression was altered in patients with idiopathic pulmonary fibrosis and secondary interstitial pneumonia compared to normal patients, and that these alterations might contribute to the pathogenesis of the disease.
Lungs from patients with idiopathic pulmonary fibrosis had a lower level of PDE4B expression than normal lungs, and the expression was greatly enhanced in lungs from patients with secondary interstitial pneumonia. This suggests that idiopathic pulmonary fibrosis and secondary interstitial pneumonitis lung may be formed from different pathologies in terms of inflammatory cell activation. The expression level of PDE4D was found to be higher in the order of normal lung < idiopathic pulmonary fibrosis < secondary interstitial pneumonia, suggesting that airway hypersensitivity may be enhanced in that order.

Free Research Field

麻酔学

Academic Significance and Societal Importance of the Research Achievements

治療法が非常に限られている間質性肺炎（特発性肺線維症や二次性間質性肺炎）の創薬ターゲットとして注目を受けているPDE4がその病態形成に関与する可能性を探り、疾患ごとの変化を明らかにしたことは、間質性肺炎の治療薬開発の可能性を広げたと言える。
現在間質性肺炎と同じ分類に属する特発性肺線維症と二次性間質性肺炎が異なる病態から成る可能性を示したことは、今後の疾患分類の枠組みに何らかの影響を与える可能性がある。