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Antibody therapy against the type-III toxin secretion system on lung infection and sepsis associated with Pseudomonas aeruuginosa

Research Project

Project/Area Number 13671604
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

SHIME Nobuaki  Kyoto Prefectural University of Medicine, Medical school, Assistant professor, 医学部, 助手 (00260795)

Co-Investigator(Kenkyū-buntansha) HASHIMOTO Satoru  Kyoto Prefectural University of Medicine, Medical school, Assocoate professor, 医学部, 助教授 (90167578)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsPseudomonas aeruginosa / Pneumonia / Sepsis / Type-III secresion / Neutralizing antibody / Therapy / 治療 / 特異的抗体 / ショック
Research Abstract

Pseudomonas aeruginosa lung infections are frequently associated with high mortality rates, particularly in patients receiving intensive care. Depending on the type III secretion phenotype, P. aeruginosa causes acute organ damage and septic physiology in P. aeruginosa lung infections. In this study, the effects of rabbit-derived polyclonal antibody against PcrV, a protein involved in the translocation of type III secreted toxins of Pseudomonas aeruginosa, was investigated in two animal models of P. aeruginosa sepsis. In a mouse survival study, the intravenous administration of anti-PcrV IgG after the airspace instillation of a lethal dose of P. aeruginosa resulted in the complete survival of the animals. In a rabbit model of septic shock associated with P. aeruginosa-induced lung injury, animals treated with anti-PcrV IgG intracheally or intravenously had significant decreases in lung injury, bacteremia, plasma TNF-α, and significant improvement in the hemodynamic parameters associated with shock compared to animals treated in a similar manner with non-specific control IgG. The administration of anti-PcrV F(ab')_2 showed protective effects comparable to whole anti-PcrV IgG. These results document that the therapeutic administration of anti-PcrV IgG blocks the type III secretion system-mediated virulence of P. aeruginosa and prevents septic shock and death, and that these protective effects are largely Fc-independent. We conclude that antibody therapy neutralizing the type III secretion system has significant potential against lethal P. aeruginosa infections

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Shime N, Sawa T, Wiener-kronish JP, et al.: "Therapeutic Administration of Anti-PcrV F(ab')_2 in Sepsis Associated with Pseudomonas Aeruginosa"J Immunol. 167(10). 5880-5886 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, Sawa T, Wiener-kronish JP, et al.: "Specific antibody therapy to PcrV is effective to prevent sepsis/septic shock associated with Pseudomonas aeruginosa pneumonia"Am J Respir Crit Care Med. 163(5). A25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, Hashimoto T, et al.: "Arterial Ketone Body Ratio (AKBR) for the Assessment of the Severity of Illness in Pediatric Patients Following Cardiac Surgery"J Crit Care. 16(3). 102-107 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, et al.: "Bioelectrical impedance analysis for the assessment of critical illness in pediatric patients following heart surgery"Crit Care Med. 30(3). 518-520 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 志馬伸朗, 橋本 悟: "ARDS/sepsisの薬物治療の展望"呼吸. 21(5). 471-476 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Faure K, Sawa T, Shime N, et al.: "Acute lung injury and death associated with cytotoxic P. Aeruginosa pneumonia in LPS-resistant C3H/HeJ mice"Am J Respir Crit Care Med. 165. A (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, Sawa T, Wiener-kronishi JP, et al: "Therapeutic Administration of Anti-PcrV F(ab')_2 in Sepsis Associated with Pseudomonas Aeruginosa"J Immunol. 167(10). 5880-5886 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, Sawa T, Wiener-kronishi JP, et al: "Specific antibody therapy to PcrV is effective to prevent sepsis/septic shock associated with Pseudomonas aeruginosa pneumonia"Am J Respir Crit Care Med. 163(5). A25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, Hashimoto S, et al: "Arterial Ketone Body Ratio (AKBR) for the Assesment of the Severity of Illness in Pediatric Patients Following Cardiac Surgery"J Crit Care. 16(3). 102-107 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, et al: "Bioelectrical impedance analysis for the assessment of critical illness in pediatric patients following heart surgery"Crit Care Med. 30(3). 518-520 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, Hashimoto S: "Pharmachological therapy for ARDS/sepsis (in Japanese)"Kokyuu. 21(5). 471-476 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Farue K, Sawa T, Shime N, et al: "Acute lung injury and death associated with cytotoxic P. Aeruginosa pneumonia in LPS-resistant C3H/HeJ mice"Am J Respir Crit Care Med. 165. A (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shime N, Sawa T, Wiener-Kronish JP, et al.: "Liver damage in Pseudomonas aeruginosa bacteremia is associated with the type-III mediated virulence"Am J Respir Crit Care Med. 167(発表予定). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Faure K, Sawa T, Shime N, et al.: "Acute lung injury and death associated with cytotoxic P. aeruginosa pneumonia in LPS-resistant C3H/HeJ mice"Am J Respir Crit Care Med. 165. A (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hiramatsu N, Shime N, et al.: "Intention Myoclonus in Paediatric Patients Following Severe Cardiopulmonary Failure : A Report of Three Cases"Critical Care and Resuscitation. 4(2). 104-106 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shime N, et al.: "Oxygen transport markers for the mortality and morbidity prediction in pediatric patients following cardiac surgery"Abstracts of the 12^<th> congress of the western pacific association of critical care medicine congress. 151-151 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 志馬伸朗, 橋本悟: "ARDS/sepsisの薬物治療の展望"呼吸. 21(5). 471-476 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 芦田ひろみ, 志馬伸朗他: "小児開心周術期おける生体インピーダンス測定の有用性"液体・代謝管理. 18(1). 47-49 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shime N, et al.: "Bilateral transient radial nerve palsies in an infant after cardiac surgery"Can J of Anesth. 48(2). 200-203 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shime N, et al.: "The application of modified sequential organ failure assessment(m/SOFA)score in children after cardiac surgery"J Cardiothorac Vasc Anesth. 15(4). 463-468 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shime N, et al.: "Arterial ketome body ratio (AKBR) for the assessment of the severity of illness in pediatric patients following cordiac surgery"J Crit Care. 16(3). 102-107 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shime N, et al.: "Therapeutic administration of anti-PcrV F_<(aid)2> in sepsis associated with Pseudomouas aeraginosa"J Immunol. 167(10). 5880-5886 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 志馬 伸朗, 他: "小児開心周術期における血中乳酸濃度による重症度評価"麻酔. 50(7). 752-757 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shime N, et al.: "Specific antibody therapy to psendomouas PcrVis effective to prevent sepsis/septic shock associated with pseudomouas aeruginosa pneumonia"Am J Resp Crit Cave Med. 163(5). A25 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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