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Elucidation of mechanism and effect of hypothermia during sepsis on granulopoiesis

Research Project

Project/Area Number 17K11573
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Emergency medicine
Research InstitutionHiroshima University

Principal Investigator

SHIME NOBUAKI  広島大学, 医系科学研究科(医), 教授 (00260795)

Co-Investigator(Kenkyū-buntansha) 平位 秀世  京都大学, 医学研究科, 助教 (50315933)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords好中球 / 分化 / 低体温 / 敗血症 / 成熟 / 感染症 / 体温
Outline of Final Research Achievements

We investigated the effect and mechanism of hypothermia associated with sepsis on host defense. In a mouse model exposed to the cold environment, the number of peripheral blood neutrophils and the number of mature neutrophils in bone marrow cells were decreased, while the number of cells in the intermediate stage between mature neutrophils and progenitor cells was increased. This was also comfirmed in the hypothermic culture model of whole bone marrow cells, and the number of neutrophils that went toward differentiation and maturation from neutrophil progenitor cells was significantly reduced. In the mouse sepsis model, the number of peripheral blood neutrophils was significantly reduced in individuals who had decreased body temperature. Effect of decreased level of aspartic acid on neutrophil differentiation was suspected using metabolome analysis. The adjusted mortality rate was significantly higher in patients with severe infections with a body temperature below 36 degrees.

Academic Significance and Societal Importance of the Research Achievements

敗血症は致死率の高い重症感染病態であるが、敗血症時において併発する低体温が生体防御能に及ぼす影響とその機序については明らかではなかった。感染防御の最前線で働くのは好中球である。低体温時における好中球の分化増殖に及ぼす影響を、生体防御能の観点より検討することは、病態生理の解明のみならず、これに立脚した新しい治療戦略を確立するための基礎的知見を提供しうる。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (34 results)

All 2020 2019 2018 2017

All Journal Article (17 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 3 results) Presentation (15 results) (of which Int'l Joint Research: 5 results,  Invited: 10 results) Book (2 results)

  • [Journal Article] 体温の生理学 その熱は下げるべきか?2020

    • Author(s)
      志馬伸朗
    • Journal Title

      INTENSIVIST

      Volume: 12 Pages: 189-194

    • Related Report
      2019 Annual Research Report
  • [Journal Article] ICUにおける発熱にどのように対処すべきか?2019

    • Author(s)
      志馬伸朗
    • Journal Title

      Hospitalist

      Volume: 7 Pages: 357-363

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Unique patterns of lower respiratory tract microbiota are associated with inflammation and hospital mortality in acute respiratory distress syndrome2019

    • Author(s)
      Kyo Michihito、Nishioka Keisuke、Nakaya Takaaki、Kida Yoshiko、Tanabe Yuko、Ohshimo Shinichiro、Shime Nobuaki
    • Journal Title

      Respiratory Research

      Volume: 20 Issue: 1 Pages: 246-246

    • DOI

      10.1186/s12931-019-1203-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 非古典的単球の生存を制御する転写因子C/EBPβ2019

    • Author(s)
      平位秀世
    • Journal Title

      医学のあゆみ

      Volume: 268 Pages: 145-146

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
  • [Journal Article] Impact of inappropriate empiric antimicrobial therapy on mortality in pediatric patients with bloodstream infection: a retrospective observational study2019

    • Author(s)
      Michihito Kyo, Shinichiro Ohshimo, Tadashi Kosaka, Naohisa Fujita and Nobuaki Shime
    • Journal Title

      J Chemother

      Volume: 31 Issue: 7-8 Pages: 388-393

    • DOI

      10.1080/1120009x.2019.1623362

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C/EBPβ is a critical mediator of IFNα-induced exhaustion of chronic myeloid leukemia stem cells.2019

    • Author(s)
      Yokota A, Hirai H, Sato R, Adachi H, Sato F, Hayashi Y, Sato A, Kamino N, Miura Y, Nakano M, Tenen DG, Kimura S, Tashiro K, Maekawa T
    • Journal Title

      Blood Advances

      Volume: 3 Issue: 3 Pages: 476-488

    • DOI

      10.1182/bloodadvances.2018020503

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical outcomes after initial treatment of methicillin-resistant Staphylococcus aureus infections2018

    • Author(s)
      Shime Nobuaki、Saito Nobuyuki、Bokui Miya、Sakane Naoki、Kamimura Mitsuhiro、Shinohara Tsutomu、Kosaka Tadashi、Ishikura Hisashi、Kobayashi Atsuko
    • Journal Title

      Infection and Drug Resistance

      Volume: Volume 11 Pages: 1073-1081

    • DOI

      10.2147/idr.s159447

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Implementation of an empirical antimicrobial protocol in a critical care setting: A single-center retrospective observational cohort study in bacteremic patients2018

    • Author(s)
      Kano Ken-ichi、Shime Nobuaki、Nishiyama Kei
    • Journal Title

      Journal of Infection and Chemotherapy

      Volume: 24 Issue: 12 Pages: 965-968

    • DOI

      10.1016/j.jiac.2018.08.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sera from Septic Patients Contain the Inhibiting Activity of the Extracellular ATP-Dependent Inflammasome Pathway2018

    • Author(s)
      Ho Van Minh、Hirohashi Nobuyuki、Kong Weng-Sheng、Yun Guo、Ota Kohei、Itai Junji、Yamaga Satoshi、Suzuki Kei、Tanigawa Koichi、Kanno Masamoto、Shime Nobuaki
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 245 Issue: 3 Pages: 193-204

    • DOI

      10.1620/tjem.245.193

    • NAID

      130007399851

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 敗血症における体温管理 「ぞんざい」だった発熱管理 いまこそ熱をアツく語ろう2018

    • Author(s)
      志馬伸朗
    • Journal Title

      LiSA

      Volume: 25 Issue: 1 Pages: 326-330

    • DOI

      10.1186/s40560-018-0306-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antimicrobials in the PICU2018

    • Author(s)
      Shime Nobuaki
    • Journal Title

      Pediatric Critical Care Medicine

      Volume: 19 Issue: 6 Pages: 581-582

    • DOI

      10.1097/pcc.0000000000001544

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 緊急時好中球造血に必須の転写因子C/EBPβによる造血幹細胞の分化増殖制御2018

    • Author(s)
      平位秀世
    • Journal Title

      臨床血液

      Volume: 59 Pages: 798-804

    • NAID

      130007393866

    • Related Report
      2018 Research-status Report
  • [Journal Article] Confounders for interpreting the benefit of a biomarker-based strategy in early discontinuation of empirical antifungal therapy.2018

    • Author(s)
      Yamaga S, Ohshimo S, Shime N, Nseir S, Sendid B, Rouze A
    • Journal Title

      Intensive Care Med

      Volume: 44 Issue: 3 Pages: 399-400

    • DOI

      10.1007/s00134-018-5068-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association between appropriate empiric antimicrobial therapy and mortality from bloodstream infections in the intensive care unit.2017

    • Author(s)
      Yamaga S, Shime N.
    • Journal Title

      J Infect Chemother

      Volume: 24 Issue: 4 Pages: 267-271

    • DOI

      10.1016/j.jiac.2017.11.011

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Proposal of a New Pediatric Sequential Organ Failure Assessment Score for Possible Validation.2017

    • Author(s)
      Shime N, Kawasaki T, Nakagawa S.
    • Journal Title

      Pediatr Crit Care Med

      Volume: 18 Issue: 1 Pages: 98-99

    • DOI

      10.1097/pcc.0000000000001009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] 発熱と解熱処置2017

    • Author(s)
      志馬伸朗
    • Journal Title

      レジデント

      Volume: 10 Pages: 21-27

    • Related Report
      2017 Research-status Report
  • [Journal Article] C/EBPβ is required for survival of Ly6C?monocytes2017

    • Author(s)
      Tamura Akihiro、Hirai Hideyo、Yokota Asumi、Kamio Naoka、Sato Atsushi、Shoji Tsukimi、Kashiwagi Takahiro、Torikoshi Yusuke、Miura Yasuo、Tenen Daniel G.、Maekawa Taira
    • Journal Title

      Blood

      Volume: 130 Issue: 16 Pages: 1809-1818

    • DOI

      10.1182/blood-2017-03-772962

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Multidimensional approach for sepsis and septic shock.2019

    • Author(s)
      Shime N.
    • Organizer
      第93回日本感染症学会総会・学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 市中敗血症における適正なEmpiric Therapyとは?2019

    • Author(s)
      志馬伸朗
    • Organizer
      第67回日本化学療法学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] C/EBPβ Isoforms Regulate Proliferation and Differentiation of Regenerating Hematopoietic Stem/Progenitor Cells.2019

    • Author(s)
      Sato A, Yokota A, HayashiY, Kamio N, SagaiS, Maekawa T and Hirai H
    • Organizer
      American Society of Hematology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] C/EBPbeta isoforms regulate hematopoietic stem cells under stress conditions.2019

    • Author(s)
      Hirai H
    • Organizer
      4th Symposium “Gene Regulation in Differentiation and Cancer”
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 救急/ICU領域における侵襲性真菌感染症2019

    • Author(s)
      志馬伸朗
    • Organizer
      日本外科感染症学会雑誌
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Recognition of low body temperature and its association with outcome in bacteremic patients admitted to emergency and critical care center2019

    • Author(s)
      Nobuaki Shime, Satoshi Yamaga
    • Organizer
      The 46th annual meeting of the Japanese Society of Intensive Care Medicine
    • Related Report
      2018 Research-status Report
  • [Presentation] 敗血症コントラバーシャル治療の現状と考え方.2018

    • Author(s)
      志馬伸朗
    • Organizer
      第92回日本感染症学会学術講演会・第66回日本化学療法学会総会合同学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 好中球分化成熟に与える低体温の影響2018

    • Author(s)
      鳥越 勇佑, 志馬 伸朗, 横田 明日美, 神尾 尚馨, 佐藤 淳至, 庄司 月美, 柏木 隆宏, 三浦 康生, 前川 平, 平位 秀世
    • Organizer
      第80回日本血液学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Impact of Hypothermia on Differentiation and Maturation of Neutrophils.2018

    • Author(s)
      Torikoshi Y, Shime N, Yokota A, Kamio N, Sato A, Shoji T, Kashiwagi T, Miura Y, Maekawa T, Hirai H
    • Organizer
      American Society of Hematology, 60th Annual Meeting and Exposition
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] C/EBPβ critically mediated IFNα-induced exhaustion of chronic myeloid leukemia stem cells.2018

    • Author(s)
      Hideyo Hirai
    • Organizer
      The 9th JSH International symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] mTOR-C/EBPβ-c-Myc Axis Regulates the Behavior of Myeloid-Biased Hematopoietic Stem Cells Under Stress Condition2017

    • Author(s)
      Sato A, Hirai H, Yokota A, Tamura A, Shoji T, Kashiwagi T, Kamio N, Torikoshi Y, Miura Y, Maekawa T
    • Organizer
      American Society of Hematology
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 抗菌薬のやめどき, やめかたを考える.2017

    • Author(s)
      志馬伸朗
    • Organizer
      日本救急医学会総会・学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 救急領域における抗菌薬の選び方2017

    • Author(s)
      志馬伸朗
    • Organizer
      日本救急医学会総会・学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 救急集中治療におけるantimicrobial/antifungal stewardship.2017

    • Author(s)
      志馬伸朗
    • Organizer
      日本感染症学会西日本地方会学術集会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Regulation of hematopoietic stem cells by C/EBPβ, a transcription factor required for emergency granulopoiesis.2017

    • Author(s)
      Hirai H
    • Organizer
      日本血液学会学術総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Book] ER・ICU 100のピットフォール2019

    • Author(s)
      志馬 伸朗
    • Total Pages
      310
    • Publisher
      中外医学社
    • ISBN
      4498166043
    • Related Report
      2019 Annual Research Report
  • [Book] ICU感染制御を究める2017

    • Author(s)
      志馬伸朗
    • Total Pages
      200
    • Publisher
      南江堂
    • ISBN
      9784524254965
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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