• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Study on the pathogenesis of severe influenza virus infection associated with cytokine storm and its effective treatment options

Research Project

Project/Area Number 16H05348
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Infectious disease medicine
Research InstitutionThe University of Tokushima

Principal Investigator

KIDO Hiroshi  徳島大学, 先端酵素学研究所(デザイン), 特任教授 (50144978)

Co-Investigator(Kenkyū-buntansha) 高橋 悦久  徳島大学, 先端酵素学研究所(デザイン), 特任助教 (10380065)
Research Collaborator SAWAFUCHI Takako  
IL INDALAO  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2018: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords感染症 / インフルエンザ / サイトカイン / ミトコンドリア / 糖代謝 / 脂質代謝 / 多臓器不全 / 血管内皮細胞 / イムノモデュレータ / マクロライド / 乳酸菌 / ウイルス / イムノモジュレーター / MMP-9 / MCP-1 / 重症化 / 代謝破綻 / サイトカインストーム / 治療薬 / トリプシン
Outline of Final Research Achievements

The pathogenesis of severe influenza virus infection is associated with “influenza─cytokine─protease” cycle and “cytokine─metabolic disorder” cycle. Among the proinflammatory cytokines, IL-1β plays a key role in suppression of mitochondrial energy metabolism, cellular functions and immunological responses of host defense. We found that inhibitor of pyruvate dehydrogenase kinase 4 in glucose metabolism and bezafibrate, stimulator of lipid metabolism, in mitochondria are effective treatment options for influenza-induced metabolic disorder in mitochondria. In addition, macrolide antibiotics and the L. bulgaricus OLL1073R-1 yogurt cultures have immune-stimulator functions as adjuvants and restored antibody production rates effectively. In this project, we clarified that these drugs and materials are useful treatment options for severe influenza virus infection and multiple organ failure.

Academic Significance and Societal Importance of the Research Achievements

人類は、新型インフルエンザや、高病原性鳥インフルエンザのパンデミックに備える必要がある。現在これらのウイルス病原体側の研究は進んでいるが、感染時の重症化する基礎疾患を持っヒトに対する重症化対策が遅れている。本研究では、インフルエンザ感染重症化の機序の詳細を明らかにし、その機序に基づく治療薬を具体的に提案しているところに学術的意義と社会的意義がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (24 results)

All 2019 2018 2017 2016

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Oral vaccination with influenza hemagglutinin combined with human pulmonary surfactant-mimicking synthetic adjuvant SF-10 induces efficient local and systemic immunity compared with nasal and subcutaneous vaccination and provides protective immunity in mice.2019

    • Author(s)
      Kimoto T, Kim H, Sakai S, Takahashi E, Kido H
    • Journal Title

      Vaccine

      Volume: 37 Issue: 4 Pages: 612-622

    • DOI

      10.1016/j.vaccine.2018.12.002

    • NAID

      120007042440

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] インフルエンザ脳症の発症メカニズム2019

    • Author(s)
      木戸 博
    • Journal Title

      呼吸器内科

      Volume: 35 Pages: 81-87

    • NAID

      40021788939

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Endogenous genetic risk factor for serious heatstroke: the thermolabile phenotype of carnitine palmitoyltransferase II variant2018

    • Author(s)
      Oda J, Yukioka T, Azuma K, Arai T, Chida J, Kido H
    • Journal Title

      Acute Med Surg

      Volume: 6 Pages: 25-29

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prion protein protects mice from lethal infection with influenza A viruses2018

    • Author(s)
      Chida Junji、Hara Hideyuki、Yano Masashi、Uchiyama Keiji、Das Nandita Rani、Takahashi Etsuhisa、Miyata Hironori、Tomioka Yukiko、Ito Toshihiro、Kido Hiroshi、Sakaguchi Suehiro
    • Journal Title

      PLOS Pathogens

      Volume: 14 Issue: 5 Pages: e1007049-e1007049

    • DOI

      10.1371/journal.ppat.1007049

    • NAID

      120006524496

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CPT-II遺伝子多型とインフルエンザ脳症の関係とは?2018

    • Author(s)
      木戸 博
    • Journal Title

      インフルエンザ診療ガイド 2018-19

      Volume: 1 Pages: 206-209

    • Related Report
      2018 Annual Research Report
  • [Journal Article] Clarithromycin suppresses induction of monocyte chemoattractant protein-1 and matrix metalloproteinase-9 and improves pathological changes in the lungs and heart of mice infected with influenza A virus2018

    • Author(s)
      Takahashi Etsuhisa、Indalao Irene L.、Sawabuchi Takako、Mizuno Keiko、Sakai Satoko、Kimoto Takashi、Kim Hyejin、Kido Hiroshi
    • Journal Title

      Comparative Immunology, Microbiology and Infectious Diseases

      Volume: 56 Pages: 6-13

    • DOI

      10.1016/j.cimid.2017.11.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Adjuvanting influenza hemagglutinin vaccine with a human pulmonary surfactant-mimicking synthetic compound SF-10 induces local and systemic cell-mediated immunity in mice2018

    • Author(s)
      Kim Hyejin、Kimoto Takashi、Sakai Satoko、Takahashi Etsuhisa、Kido Hiroshi
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 1 Pages: 1-15

    • DOI

      10.1371/journal.pone.0191133

    • NAID

      120006812010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines.2018

    • Author(s)
      Hayashi H, Kubo Y, Izumida M, Takahashi E, Kido H, Sato K, Yamaya M, Nishimura H, Nakayama K, Matsuyama T.
    • Journal Title

      Front Cell Infect Microbiol

      Volume: 8 Pages: 91-91

    • DOI

      10.3389/fcimb.2018.00091

    • NAID

      120006937672

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 宿主因子を標的にした新たなインフルエンザ治療の試み2018

    • Author(s)
      千田淳司、木戸博、坂口末廣
    • Journal Title

      BIO Clinica

      Volume: 33 Pages: 256-259

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Anti-influenza virus activity of extracts from stems of Jatropha multifida Linn. collected in Myanmar2017

    • Author(s)
      M. Shoji, S. Woo, A. Masuda, N. N. Win, H. Ngwe, E. Takahashi, H. Kido, H. Morita, T. Ito.
    • Journal Title

      BMC Complem Altern Med

      Volume: 17 Issue: 1 Pages: 96-96

    • DOI

      10.1186/s12906-017-1612-8

    • NAID

      120006814109

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] インフルエンザ感染の重症化機序と治療、効果的な経鼻、経口ワクチン開発2017

    • Author(s)
      木戸 博
    • Journal Title

      消化と吸収

      Volume: 39 Pages: 72-77

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Energy metabolic disorder is a major risk factor in severe influenza virus infection. Proposals for new therapeutic options based on animal model experiments.2016

    • Author(s)
      Kido H, Indalao IL, Kim H, Kimoto T, Sakai S, Takahashi E
    • Journal Title

      Respir Investg

      Volume: 54 Pages: 312-319

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] IL-1 beta is a key cytokine which induces trypsin upregulation in influenza virus-cytokine-trypsin cycle2016

    • Author(s)
      Indalao IK, Sawabuchi T, Takahashi E, Kido H.
    • Journal Title

      Arch Virol

      Volume: 162 Issue: 1 Pages: 201-211

    • DOI

      10.1007/s00705-016-3093-3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] The interplay between inflammation and FAOD in the pathogenesis of infection associated encephalopathy2018

    • Author(s)
      Kido H
    • Organizer
      International Network for Fatty Acid Oxidation Research and Management
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] SF-10 adjuvant derived from pulmonary surfactant enhances incorporation of antigens into intestinal antigen presenting cells and induces antigen specific immunities.2018

    • Author(s)
      Kimoto T, Sakai S, Kameda K, Takahashi E, Kido H
    • Organizer
      第54 回日本肺サーファクタント・界面医学界
    • Related Report
      2018 Annual Research Report
  • [Presentation] A型インフルエンザ感染においてマクロライド薬は単球走化性タンパク質(MCP-1)産生を抑制し感染局所の炎症性細胞浸潤を軽減すると共に、長期免疫メモリーを増強する2018

    • Author(s)
      高橋 悦久、澤淵 貴子、木戸 博
    • Organizer
      第25回マクロライド新作用研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] インフルエンザ感染モデル動物実験法2018

    • Author(s)
      高橋 悦久、木戸 博
    • Organizer
      第25回マクロライド新作用研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肺サーファクタント由来人工合成SF-10アジュバントは、小腸粘膜の抗原提示細胞への抗原取り込みを増強し、消化管と気道粘膜の抗原特異的抗体産生細胞を誘導する2018

    • Author(s)
      木本 貴士、堺 聡子、亀田 桂子、高橋 悦久、木戸 博
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] インフルエンザウイルスの感染・増殖性を決定する宿主プロテアーゼの同定と、この研究がもたらした重症化機序の解明と経鼻ワクチン開発2017

    • Author(s)
      木戸博
    • Organizer
      第22回日本病態プロテアーゼ学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] インフルエンザ感染により発現増加するMMP-9とMCP-1はクラリスロマイシンの経口投与により抑制され、炎症が軽減される2017

    • Author(s)
      高橋悦久、澤淵貴子、木本貴士、堺聡子、木戸博
    • Organizer
      第22回日本病態プロテアーゼ学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] インフルエンザAウイルス感染においてクラリスロマイシン投与によりMMP-9とMCP-1の発現誘導が抑制され、肺と心臓の炎症が軽減される2017

    • Author(s)
      高橋悦久、澤淵貴子、木本貴士、堺聡子、木戸博
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Trypsin upregulation is mainly affected by IL-1β in influenza-cytokine protease cycle2016

    • Author(s)
      Indalao IK, Sawabuchi T, Takahashi E, Kido H.
    • Organizer
      日本生化学会
    • Place of Presentation
      東北大学 川内キャンパス(宮城県仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] IL-1 beta; signaling induces trypsin upregulation in influenza virus-cytokine-trypsin cycle in multiple organ failure by infection2016

    • Author(s)
      Indalao IK, Sawabuchi T, Takahashi E, Kido H.
    • Organizer
      Option IX
    • Place of Presentation
      Chicago, Sheraton Grand Chicago, USA
    • Year and Date
      2016-08-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Trypsin upregulation is mainly affected by IL-1β in influenza-cytokine protease cycle2016

    • Author(s)
      Indalao IK, Sawabuchi T, Takahashi E, Kido H.
    • Organizer
      日本病態プロテアーゼ学会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府豊中市)
    • Year and Date
      2016-08-05
    • Related Report
      2016 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi