Study of the therapeutic agent for the treatment of highly pathogenic influenza

• Project/Area Number: 25670465
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Infectious disease medicine
• Research Institution: Okayama University
• Principal Investigator: MORISHIMA Tsuneo 岡山大学, 医歯(薬)学総合研究科, 特命教授 (90157892)
• Research Collaborator: FUJI Yousuke 岡山大学, 大学院医歯薬学総合研究科小児急性疾患学講座, 助教 (80549775) ; TSUGE Mitsuru 松山赤十字病院, 小児科 (80625004)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: インフルエンザ / 肺炎 / HMGB-1 / チオレドキシン / H5N1 / 脳症 / AH7N9 / ARDS / 喘息 / H1N1pdm

Outline of Final Research Achievements

The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment for influenza A virus (H1N1)-induced pneumonia in mice.Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lung of H1N1-inoculated mice; which was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.

Research Products

• [Journal Article] Brain magnetic resonance imaging in acute phase of pandemic influenza A (H1N1) 2009-associated encephalopathy in children. (2015)
  • Author(s): Ishida Y, Kawashima H, Morichi S, Yamanaka G, Okumura A, Nakagawa S, Morishima T
  • Journal Title: Neuropediatrics Volume: 46(1) Issue: 01 Pages: 20-5
  • DOI: 10.1055/s-0034-1393708
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis， (2014)
  • Author(s): Tsuge M1, Oka T, Yamashita N, Saito Y, Fujii Y, Nagaoka Y, Yashiro M, Tsukahara H, Morishima T.
  • Journal Title: J Neurovirol. Volume: 20 Issue: 1 Pages: 73-84
  • DOI: 10.1007/s13365-013-0231-5
  • Peer Reviewed
• [Journal Article] Cytokine profile of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during seasonal H1N1 infection. (2014)
  • Author(s): Hasegawa S, Wakiguchi H, Okada S, Gui Kang Y, Fujii N, Hasegawa M, Hasegawa H, Ainai A, Atsuta R, Shirabe K, Toda S, Wakabayashi-Takahara M, Morishima T, Ichiyama T.
  • Journal Title: Cytokine Volume: 69(2) Issue: 2 Pages: 206-10
  • DOI: 10.1016/j.cyto.2014.06.006
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Analysis of bronchoalveolar lavage fluid in a mouse model of bronchial asthma and H1N1 2009 infection. (2013)
  • Author(s): Okada S, Hasegawa S, Hasegawa H, Ainai A, Atsuta R, Ikemoto K, Sasaki K, Toda S, Shirabe K, Takahara M, Harada S, Morishima T, Ichiyama T.
  • Journal Title: Cytokine. Volume: 63 Pages: 194-200
  • Peer Reviewed
• [Journal Article] Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling. (2013)
  • Author(s): Yamashita N, Tsukahara H, Tsuge M, Nagaoka Y, Yashiro M, Saito Y, Fujii Y, Oka T, Morishima T.
  • Journal Title: Pediatr Int. Volume: 55 Pages: 572-7
  • Peer Reviewed
• [Presentation] 急性脳症におけるCOX2 のDNA メチル化の関与 (2014)
  • Author(s): 藤井 洋輔
  • Organizer: 第62回日本ウイルス学会学術集会
  • Place of Presentation: 神奈川 パシフィコ横浜会議センター
  • Year and Date: 2014-11-11
• [Presentation] 痙攣重責を示したインフルエンザA（H1N1）pdm及びロタウイルス胃腸炎の宿主遺伝子発現の解析 (2014)
  • Author(s): 津下 充
  • Organizer: 第46回日本小児感染症学会
  • Place of Presentation: 東京 京王プラザホテル
  • Year and Date: 2014-10-19
• [Book] Oxidative Stress in Applied Basic Research and Clinical Practice - Pediatric Disorders (2014)
  • Author(s): Yashiro M, Tsukahara H, Morishima T.
  • Publisher: Springer