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Immune modulating therapy to restore impaired innate immunity in patients with sepsis or after surgery

Research Project

Project/Area Number 23249072
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionThe University of Tokyo

Principal Investigator

Yamada Yoshitsugu  東京大学, 医学部附属病院, 教授 (30166748)

Co-Investigator(Kenkyū-buntansha) SETO Yasuyuki  東京大学, 医学部附属病院, 教授 (00260498)
NAKAJIMA Susumu  東京大学, 医学部附属病院, 准教授 (40323597)
MATSUBARA Takehiro  東京大学, 医学部附属病院, 特任講師 (40361498)
CHO Kyohiro  東京大学, 医学部附属病院, 講師 (50302708)
YAHAGI Naoki  東京大学, 医学部附属病院, 教授 (60158045)
UCHIDA Kanji  東京大学, 医学部附属病院, 准教授 (60302709)
YAGI Koichi  東京大学, 医学部附属病院, 助教 (90422310)
森 和彦  東京大学, 医学部附属病院, 講師 (10436470)
Project Period (FY) 2011-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥47,060,000 (Direct Cost: ¥36,200,000、Indirect Cost: ¥10,860,000)
Fiscal Year 2015: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Fiscal Year 2014: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2013: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2012: ¥10,140,000 (Direct Cost: ¥7,800,000、Indirect Cost: ¥2,340,000)
Fiscal Year 2011: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Keywords敗血症 / 急性呼吸窮迫症候群 / サイトカイン / 生体防御 / インターフェロンβ / 免疫賦活 / バイオマーカ / 免疫抑制 / 重症感染症 / 免疫強化療法 / 顆粒球マクロファージコロニー刺激因子 / バイオマーカー / 顆粒球マクロファージコロニー刺激因子
Outline of Final Research Achievements

Sepsis and sepsis associated acute respiratory distress syndrome are diseases with high mortality without effective treatment options. Controversies to its pathogenesis and heterogeneity of the patient population are thought to be the failure of multiple clinical trials mainly aims to modulate hyperimmune state.
Retrospective analysis of parameters from patients admitted in the intensive care unit (ICU) in a single institute revealed that lower mean arterial pressure, white blood cell / platelet count, and higher serum lactate dehydrogenase on 1 day after ICU admission associated with in-hospital death. Mouse model of peritoneal sepsis induced by cecal ligation and puncture revealed that septic mice fell into immune compromised state 4-days after CLP and were susceptible to death following nosocomial infection. Systemic interferon beta improved survival of septic pneumonia model and may work to restore impaired innate immunity.

Report

(6 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (46 results)

All 2016 2015 2014 2013 2012 2011

All Journal Article (17 results) (of which Peer Reviewed: 13 results,  Acknowledgement Compliant: 2 results,  Open Access: 1 results) Presentation (28 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] 誤嚥性肺炎の病態と治療2016

    • Author(s)
      内田寛治
    • Journal Title

      麻酔

      Volume: 65 Pages: 13-22

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Recovery from extreme hemodilution (hemoglobin level of 0.6g/dL) in cadaveric liver transplantation.2015

    • Author(s)
      Kariya T, Ito N, Kitamura T, Yamada Y.
    • Journal Title

      Anesthesia and analgesia case report

      Volume: 10 Issue: 10 Pages: 132-134

    • DOI

      10.1213/xaa.0000000000000132

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A standardized blood test for the routine clinical diagnosis of impaired GM-CSF signaling using flow cytometry.2014

    • Author(s)
      Kusakabe Y, Uchida K, Hiruma T, Suzuki Y, Totsu T, Suzuki T, Carey BC, Yamada Y, Trapnell BC.
    • Journal Title

      J Immunol Methods.

      Volume: 413 Pages: 1-11

    • DOI

      10.1016/j.jim.2014.07.009

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Up-Regulation of Cluster of Differentiation (CD) 11b Expression on the Surface of Canine Granulocytes with Human Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF).2014

    • Author(s)
      Nakagaki K, Nunomura Y, Uchida K, Nakata K, Tazawa R
    • Journal Title

      Journal of Veterinary Medical Science

      Volume: 76 Pages: 1173-6

    • NAID

      130004432194

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Remifentanil on In-hospital Mortality and Length of Stay Following Clipping of Intracranial Aneurysm: A Propensity Score Matched Analysis.2014

    • Author(s)
      Uchida K, Yasunaga H, Sumitani M, Horiguchi H, Fushimi K, Yamada Y
    • Journal Title

      Journal of Neurosurgical Anesthesiology

      Volume: 26 Issue: 4 Pages: 291-8

    • DOI

      10.1097/ana.0000000000000039

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Standardized serum GM-CSF autoantibody testing for the routine clinical diagnosis of autoimmune pulmonary alveolar proteinosis2014

    • Author(s)
      Uchida K, Nakata K, Carey B, Chalk C, Suzuki T, Sakagami T, Koch DE, Stevens C, Inoue Y, Yamada Y, Trapnell BC.
    • Journal Title

      J Immunol Methods

      Volume: 402 Issue: 1-2 Pages: 57-70

    • DOI

      10.1016/j.jim.2013.11.011

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Perioperative factors affecting the occurrence of acute complex regional pain syndrome following limb bone fracture surgery: data from the Japanese Diagnosis Procedure Combination database.2014

    • Author(s)
      Sumitani M, Yasunaga H, Uchida K, Horiguchi H, Nakamura M, Ohe K, Fushimi K, Matsuda S, Yamada Y
    • Journal Title

      Rheumatology

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of Remifentanil on In-Hospital Mortality and Length of Stay Following Clipping of Intracranial Aneurysm: A Propensity Score-matched Analysis.2014

    • Author(s)
      Uchida K, Yasunaga H, Sumitani M, Horiguchi H, Fushimi K, Yamada Y
    • Journal Title

      J Neurosurg Anesthesiol

      Volume: in press

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 顆粒球マクロファージコロニー刺激因子(GM-CSF)シグナルと生体防御・臓器保護2013

    • Author(s)
      内田寛治
    • Journal Title

      麻酔

      Volume: 62 Pages: 265-274

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of remifentanil use on early postoperative outcomes following brain tumor resection or rectal cancer surgery.2012

    • Author(s)
      Uchida K
    • Journal Title

      Journal of Anesthesia

      Volume: 26 Issue: 5 Pages: 711-720

    • DOI

      10.1007/s00540-012-1397-3

    • NAID

      10031123494

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of cytotoxicity induced by proinflammatory cytokines in the human alveolar epithelial cell line A549.2012

    • Author(s)
      Muroya M
    • Journal Title

      BioScience Trends

      Volume: 6(2) Pages: 70-80

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Standardization of perioperative management on hepato-biliary-pancreatic surgery.2012

    • Author(s)
      Gao J
    • Journal Title

      Drug Discoveries & Therapeutics

      Volume: 6(2) Pages: 108-111

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 手術患者リスク評価と周術期管理に関連した周術期アウトカム2012

    • Author(s)
      内田 寛治
    • Journal Title

      麻酔

      Volume: 61 Pages: 514-525

    • Related Report
      2012 Annual Research Report
  • [Journal Article] The Involvement of Adenosine Triphosphate-Sensitive Potassium Channe ls in the Different Effects of Sevoflurane and Propofol on Glucose Metabolism in Fed Rats2012

    • Author(s)
      Kitamura T, Yamada Y, et al.
    • Journal Title

      Anesthesia & Analgesia

      Volume: 114 Pages: 110-116

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impact of remifentanil introduction on practice patterns in general anesthesia2011

    • Author(s)
      Uchida K, Yamada Y, et al.
    • Journal Title

      Journal of Anesthesia

      Volume: 25(PubMed-in process) Pages: 864-71

    • NAID

      10030448824

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prevalence of malignant hyperthermia and relationship with anesthetics in Japan : Data from the Diagnosis Procedure Combination Database2011

    • Author(s)
      Sumitani M, Uchida K, Yamada Y, et al.
    • Journal Title

      Anesthesiology

      Volume: 114(PubMed-indexed for MEDLINE) Pages: 84-90

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 全身麻酔のメカニズムの解明はどこまで進んだか?2011

    • Author(s)
      山田芳嗣
    • Journal Title

      麻酔

      Volume: 60 Pages: 530-533

    • Related Report
      2011 Annual Research Report
  • [Presentation] Possible systemic immune paralysis in patients undergoing aseptic, limited surgical stress2016

    • Author(s)
      Y. Tamai, K. Uchida, Y. Kusakabe, K. Chang, S. Taketomi, H. Inui, S. Tanaka, Y. Yamada
    • Organizer
      American Thoracic Society Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2016-05-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Peritoneal sepsis impairs efficient recruitment of neutrophils into the alveolar space and augment lung injury after nosocomial infection2016

    • Author(s)
      T. Hiruma, K. Uchida, B.C. Trapnell, Y. Kusakabe, Y. Yamamura, T. Totsu, K. Chang, K. Nakamura, K. Doi, S. Nakajima, N. Yahagi, Y. Yamada
    • Organizer
      American Thoracic Society Annual Meeting
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2016-05-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 敗血症に引き続く緑膿菌肺炎のマウスモデルに対するインターフェロンβの治療的効果とそのメカニズム.2015

    • Author(s)
      比留間 孝広, 内田 寛治, 日下部 良臣, 山村 睦朗, 矢作 直樹, 山田 芳嗣.
    • Organizer
      日本麻酔科学会学術集会
    • Place of Presentation
      神戸ポートピアホテル 兵庫県神戸市
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肺傷害発症と重症化のメカニズム―臨床応用への可能性―肺血管透過性の関与とその制御.2015

    • Author(s)
      内田寛治.
    • Organizer
      日本麻酔科学会学術集会
    • Place of Presentation
      神戸ポートピアホテル 兵庫県神戸市
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 院内感染マウスモデルにおけるインターフェロンβを用いた炎症制御2014

    • Author(s)
      比留間孝広
    • Organizer
      日本救急医学会
    • Place of Presentation
      福岡市
    • Year and Date
      2014-10-28 – 2014-10-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] Protective Effect Of Interferon Beta To Murine Polymicrobial Sepsis May Not Be Explained By Simple Immunesuppression2014

    • Author(s)
      Yoshiomi Kusakabe, , Kanji Uchida, Tokie Totsu, Yoko Suzuki, Takahiro Hiruma, Kent Doi, Yoshiro Yamamura, Yoshitsugu Yamada
    • Organizer
      American Thoracic Society Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2014-05-16 – 2014-05-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] Interferon Beta Improved Survival Of Septic Pneumonia Induced By Intratracheal Instillation Of Pseudomonas Aeruginosa By Increasing Neutrophil Recruitment Into The Lung2014

    • Author(s)
      Takahiro Hiruma, Kanji Uchida, Yoshiomi Kusakabe, Yoshiro Yamamura, Kensuke Nakamura, Kent Doi, Yoko Suzuki, Tokie Totsu, Susumu Nakajima, Naoki Yahagi, Yoshitsugu Yamada,
    • Organizer
      American Thoracic Society Annual Meeting
    • Place of Presentation
      San Diego
    • Year and Date
      2014-05-16 – 2014-05-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] マウス敗血症モデルに対するインターフェロンβの効果は単純な免疫抑制効果によらない2014

    • Author(s)
      日下部 良臣, 内田 寛治, 比留間 孝広, 山村 睦朗, 山田 芳嗣
    • Organizer
      日本麻酔科学会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 2次感染モデル(回盲部結紮穿孔後の肺炎)に対するインターフェロンβの効果2014

    • Author(s)
      比留間 孝広, 内田 寛治, 日下部 良臣, 山村 睦朗, 中島 勧, 山田 芳嗣
    • Organizer
      日本麻酔科学会
    • Place of Presentation
      横浜市
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 回盲部結紮穿孔後の生体防御能低下に対するインターフェロンβの効果2014

    • Author(s)
      比留間孝広,内田寛治,日下部良臣,中村謙介,井口竜太,山村睦朗,松原全宏,中島勧,山田芳嗣, 矢作直樹
    • Organizer
      第41回日本集中治療医学会
    • Place of Presentation
      京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 炎症性サイトカインで誘導される細胞障害に対する長鎖不飽和脂肪酸の細胞保護作用2014

    • Author(s)
      張京浩,山田芳嗣
    • Organizer
      第41回日本集中治療医学会
    • Place of Presentation
      京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 休日緊急手術後ICU管理を要した患者の予後因子の検討2014

    • Author(s)
      久良木ルーテ彩来,長友香苗,日下部良臣,穂積淳,松原全宏,土井研人,石井健,矢作直樹,山田芳嗣
    • Organizer
      第41回日本集中治療医学会
    • Place of Presentation
      京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 手術件数、長時間手術件数増加とICUの必要性2014

    • Author(s)
      朝元雅明,小松孝美,折井亮,山田芳嗣
    • Organizer
      第41回日本集中治療医学会
    • Place of Presentation
      京都市
    • Related Report
      2013 Annual Research Report
  • [Presentation] Effect Of Interferon Beta On Survival For Murine Polymicrobial Sepsis2013

    • Author(s)
      Yoshiomi Kusakabe, Kanji Uchida, Yoshiro Yamamura, Yoko Suzuki, Takahiro Hiruma, Yoshitsugu Yamada
    • Organizer
      American Thoracic Society Annual Meeting
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Use Of Serum GM-CSF For Diagnosis Of Patients With Hereditary Pulmonary Alveolar Proteinosis2013

    • Author(s)
      Brenna Carey, Christopher Heald, Claudia Chalk, Takuji Suzuki, Kanji Uchida, Bruce Trapnell
    • Organizer
      American Thoracic Society Annual Meeting
    • Place of Presentation
      Philadelphia, PA, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] マウス敗血症モデルでインターフェロンβは生存率を改善する2013

    • Author(s)
      日下部良臣,内田寛治,鈴木洋子,山村睦朗,比留間孝広,山田芳嗣
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      札幌市
    • Related Report
      2013 Annual Research Report
  • [Presentation] 救命救急センターICUにおける敗血症予後因子の検討2013

    • Author(s)
      長友 香苗
    • Organizer
      日本集中治療医学会第40回学術集会
    • Place of Presentation
      長野県松本文化会館他(松本市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肺胞蛋白症の全肺洗浄の麻酔;全国疫学調査の結果2012

    • Author(s)
      岡上 泰子
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      神戸国際会議場他(神戸市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] GM-CSF刺激による好中球のCD11bの上昇率で術後患者や重症感染症患者の免疫能を評価する2012

    • Author(s)
      日下部 良臣
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      神戸国際会議場他(神戸市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 肝肺症候群を有する生体肝移植症例の検討2012

    • Author(s)
      尾藤 まりあ
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      神戸国際会議場他(神戸市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] 医療コストのフィードバックを用いた医療コスト教育の試み2012

    • Author(s)
      冨岡 俊也
    • Organizer
      日本麻酔科学会第59回学術集会
    • Place of Presentation
      神戸国際会議場他(神戸市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Validation And Mechanism Of Flow-Based Whole Blood Assay To Evaluate Phagocyte Immune Function2012

    • Author(s)
      Kusakabe Y
    • Organizer
      American thoracic society annual meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dried Blood Spot Card Testing For Diagnostic, Epidemiological And Longitudinal Evaluation Of Pulmonary Alveolar Proteinosis: The US National PAP Registry Study2012

    • Author(s)
      Carey B
    • Organizer
      American thoracic society annual meeting
    • Place of Presentation
      San Francisco, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] 全身麻酔下帝王切開術の1施設における疫学2012

    • Author(s)
      池田 貴充
    • Organizer
      日本臨床麻酔学会
    • Place of Presentation
      ビッグパレット福島他(郡山市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] MRIを用いた経口補水液の種類による胃消失時間の違いの検討2012

    • Author(s)
      中村 誠
    • Organizer
      日本臨床麻酔学会
    • Place of Presentation
      ビッグパレット福島他(郡山市)
    • Related Report
      2012 Annual Research Report
  • [Presentation] レミフェンタニルを使用した麻酔の術後予後に与える影響;脳腫瘍手術と大腸手術2011

    • Author(s)
      内田寛治、住谷昌彦、康永秀生、宮田裕章、山田芳嗣
    • Organizer
      日本麻酔科学会第58回学術集会
    • Place of Presentation
      神戸市
    • Year and Date
      2011-05-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] Can Specific Anesthetic Drug Affect Postoperative Eecovery? From The Analysis Of Large Administrative Claim Database In Japan2011

    • Author(s)
      Uchida K, Yamada Y, et al.
    • Organizer
      American Thoracic Society 2011 annual meeting
    • Place of Presentation
      デンバー、コロラド州、米国
    • Year and Date
      2011-05-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Towards Global Standardization Of Serologic Blood Testing For The Diagnosis Of Autoimmune Pulmonary Alveolar Proteinosis2011

    • Author(s)
      Uchida K, Yamada Y, et al.
    • Organizer
      American Thoracic Society 2011 annual meeting
    • Place of Presentation
      デンバー、コロラド州、米国
    • Year and Date
      2011-05-15
    • Related Report
      2011 Annual Research Report
  • [Book] AEDSにおける肺保護戦略。Annual Review呼吸器2012(永井厚志他編)2012

    • Author(s)
      山田芳嗣
    • Total Pages
      270
    • Publisher
      中外医学社
    • Related Report
      2011 Annual Research Report

URL: 

Published: 2011-06-18   Modified: 2019-07-29  

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