Basic research to elucidate the function of the novel cytokine IL-38 and development of new therapeutic agents

• Project/Area Number: 19K08636
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kurume University
• Principal Investigator: Tominaga Masaki 久留米大学, 医学部, 教授 (70597773)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: IL38 / IL-38 / 肺線維症 / ブレオマイシン / 肺障害 / エラスターゼ / IL-38ノックアウトマウス / 肺障害モデル / 間質性肺疾患 / 急性肺障害

Outline of Research at the Start

本研究では、間質性肺疾患及び薬剤性肺障害における新規炎症性サイトカインIL-38 の機能を解明することで、間質性肺疾患、薬剤性肺障害とりわけ抗がん剤による薬剤性肺障害における病勢の把握や予後を推測するマーカーとして活用できることを目的とし、さらには治療法の確立していない間質性肺疾患における「新規の希少疾病用医薬品 (Orphan Drug）の開発」の基盤的研究を行う。

Outline of Final Research Achievements

A model of acute lung injury caused by bleomycin (BLM) was created and compared between the control and IL-38KO mouse groups, with the expectation that the degree of lung injury would be stronger than usual in the IL-38KO group.
BLM 20 μg was administered intratracheally, and cell count and fractionation measurements of BAL fluid on Day 21 and serum IL-38, TNFα, TGFβ, IL-4, IL13, IL-18, IL-1b, IL-17, IL-38, IL-13, IL-18, IL-1b, and IL-17 were measured. No significant differences were observed between the WT and IL38KO groups. However, the degree of inflammatory cell infiltration in the IL-38KO group was slightly less than that in the WT group.

Academic Significance and Societal Importance of the Research Achievements

IL38は活動性の高い間質性肺疾患で高発現していることをすでに発表した。そこで間質性肺疾患の線維化に対しIL38がどのように関与しているか調べるための実験であり、IL-38KO群では通常より肺障害の程度が強くなると予想していた。しかし、予想に反して炎症性サイトカインにWTとIL38KO群とで有意差を認めず、組織ではIL-38KO群で炎症細胞浸潤の程度がやや軽かった。IL38は、線維化が進んでしまうと発現は低下していたが、間質性肺疾患の活動性の炎症の時期においても、その時期によって発現に差があるのではないかと推測している。

Research Products

• [Journal Article] A Rare Case of Diffuse Bilateral Minute Pulmonary Meningothelial-like Nodules Increasing over the Short Term and Resembling Metastatic Lung Cancer (2023)
  • Author(s): Murata D, Zaizen Y, Tokisawa S, Matama G, Chikasue T, Nishii Y, Ohno S, Tsumura K, Tominaga M, Fukuoka J, Fujimoto K, Hoshino T.
  • Journal Title: Internal Medicine Volume: 62 Issue: 8 Pages: 1207-1211
  • DOI: 10.2169/internalmedicine.0343-22
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2023-04-15
  • Peer Reviewed / Open Access
• [Journal Article] Granulomatous Lymphocytic Interstitial Lung Disease in Multiple Myeloma (2023)
  • Author(s): Sasaki Jun、Tominaga Masaki、Sudou Misa、Tokisawa Saeko、Nishii Yuuya、Zaizen Yoshiaki、Matama Goushi、Chikasue Tomonori、Fujimoto Kiminori、Tabata Kazuhiro、Fukuoka Junya、Takemura Tamiko、Kawayama Tomotaka、Hoshino Tomoaki
  • Journal Title: Internal Medicine Volume: 62 Issue: 3 Pages: 439-444
  • DOI: 10.2169/internalmedicine.9758-22
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2023-02-01
  • Peer Reviewed / Open Access
• [Journal Article] Cerebrotendinous xanthomatosis with radiological abnormalities of the chest (2023)
  • Author(s): Zaizen Y, Tominaga M, Nagata S, Hoshino T.
  • Journal Title: BMJ Case Rep. Volume: 2021 Issue: 9 Pages: e243715-e243715
  • DOI: 10.1136/bcr-2021-243715
  • Peer Reviewed / Open Access
• [Journal Article] A Cluster of Paragonimiasis with Delayed Diagnosis Due to Difficulty Distinguishing Symptoms from Post-COVID-19 Respiratory Symptoms: A Report of Five Cases (2023)
  • Author(s): Sasaki Jun、Matsuoka Masanobu、Kinoshita Takashi、Horii Takayuki、Tsuneyoshi Shingo、Murata Daiki、Takaki Reiko、Tominaga Masaki、Tanaka Mio、Maruyama Haruhiko、Kawayama Tomotaka、Hoshino Tomoaki
  • Journal Title: Medicina Volume: 59 Issue: 1 Pages: 137-137
  • DOI: 10.3390/medicina59010137
  • Peer Reviewed / Open Access
• [Journal Article] Airway hyperresponsiveness and inflammation in Japanese patients with human immunodeficiency virus 1 infection (2022)
  • Author(s): Yano Chiyo、Tominaga Masaki、Naito Yoshiko、Tokunaga Yoshihisa、Kinoshita Takashi、Sasaki Jun、Okamoto Masaki、Yaita Kenichiro、Obara Hitoshi、Kakuma Tatsuyuki、Hoshino Tomoaki、Kawayama Tomotaka
  • Journal Title: Journal of Infection and Chemotherapy Volume: 28 Issue: 3 Pages: 426-433
  • DOI: 10.1016/j.jiac.2021.12.001
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Characteristics of Anti-TIF-1γ Antibody-Positive Dermatomyositis Associated with Malignancy (2022)
  • Author(s): Yumi Harada, Masaki Tominaga, Eriko Iitoh, Shinjiro Kaieda, Takuma Koga, Kiminori Fujimoto, Tomonori Chikasue, Hitoshi Obara, Tatsuyuki Kakuma, Hiroaki Ida, Totmoaka Kawayama, Tomoaki Hoshino
  • Journal Title: Journal of Clinical Medicine Volume: 11 Issue: 7 Pages: 1-10
  • DOI: 10.3390/jcm11071925
  • Peer Reviewed / Open Access
• [Journal Article] Sensitivity of transbronchial lung cryobiopsy in the diagnosis of different interstitial lung diseases (2022)
  • Author(s): Zaizen Y, Tachibana Y, Ozasa M, Yamano Y, Takei R, Kohashi Y, Kataoka K, Saito Y, Tabata K, Okamoto M, Tominaga M, Fujimoto K, Sakamoto N, Ashizawa K, Mukae H, Bychkov A, Johkoh T, Hoshino T, Kondoh Y, Fukuoka J.
  • Journal Title: Sci Rep Volume: 21 Issue: 1 Pages: 22037-22037
  • DOI: 10.1038/s41598-022-26510-6
  • Peer Reviewed / Open Access
• [Presentation] 経気管支氷結肺生検を用いた病理診断と検査有害事象 (2023)
  • Author(s): 梅元崇志、財前圭晃、真玉豪士、富永正樹
  • Organizer: 日本呼吸器学会
• [Presentation] 当院における肺術後間質性肺疾患急性増悪の検討 (2023)
  • Author(s): 光井遥佑、財前圭晃、真玉豪士、富永正樹
  • Organizer: 日本呼吸器学会
• [Presentation] 成人で見つかった慢性皮膚粘膜カンジダ症の1例 (2023)
  • Author(s): 河合真季、富永正樹、安藤みや、西小森 隆太、木下 隆、松岡昌信、川山智隆、星野友昭
  • Organizer: 日本内科学会
• [Presentation] 肉眼所見に乏しかった悪性胸膜中皮腫の2例 (2022)
  • Author(s): 桑原 七緒、富永 正樹、古垣 浩一、木下 隆、川山 智隆、星野 友昭
  • Organizer: 日本呼吸器学会地方会
• [Presentation] インフリキシマブ治療中に発症したヒラタケによる過敏性肺炎の1例 (2022)
  • Author(s): 江﨑光世、富永正樹、佐々木潤、時澤冴子、首藤美佐、西井裕哉、財前圭晃、川山智隆、星野友昭
  • Organizer: 日本呼吸器学会地方会