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2006 Fiscal Year Final Research Report Summary

Tailor-made therapy for patients with septic multiple organ failure using a cytokine adsorbing column based on genetic analysis of cytokine related gene polymorphisms

Research Project

Project/Area Number 16390514
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Emergency medicine
Research InstitutionChiba University

Principal Investigator

ODA Shigeto  Chiba University, Graduate School of Medicine, professor, 大学院・医学研究院, 教授 (90204205)

Co-Investigator(Kenkyū-buntansha) HIRASAWA Hiroyuki  Chiba University, School of Medicine, Professor Emeritus, 名誉教授 (80114320)
SADAHIRO Tomohito  Chiba University, School of Medicine, Assitant Professo, 医学部附属病院, 講師 (00436437)
NAKAMURA Masataka  Chiba University, Graduate School of Medicine, Research Associate, 大学院・医学研究院, 医員 (30315436)
MORITA Yasumasa  Chiba University, School of Medicine, Research Associate, 医学部附属病院, 医員 (20400971)
OSHIMA Taku  Chiba University, School of Medicine, Research Associate (50375789)
Project Period (FY) 2004 – 2006
Keywordsgenetic polymorphism / cytokine / hypercytokinemia / septic multiple organ failure / genetic high resk / cytokine adsorbing column / tailor-made therapy
Research Abstract

This study was conducted to establish a novel tailor-made therapy for prevention of septic multiple organ failure (MOF) with anti-cytokine strategy, such as an cytokine adsorbing column, based on the screening of genetically high risk patients of hypercytokinemia using an genetic analysis of cytokine-related genes. To identify the highly related genetic polymorphisms with hypercytokinemia, various reported genetic polymorphisms were analyzed in patients with hypercytokinemia in relation to their clinical course and outcome. Among genetic polymorphisms tested, TNF α-308G/A, IL-1β-511T/A, IL-1ra VNTR polymorphisms were identified to be highly related with uncontrolled hypercytokinemia and poor outcome. We established the screening system to analyze these polymorphisms using real-time PCR in the laboratory within 4-6 hours. To develop a more effective cytokine modulator than PMMA-CHDF, the phase II clinical trial of a newly developed cytokine adsorbing column, CYT-860, in patients with persistent and severe hypercytokinemia was conducted and has been completed. CYT-860-DHP showed significant reduction in cytokine blood levels and resulted in improvement of P/F ratio. Four of 7 enrolled patients were survived and no adverse effect was observed. Further study is needed for clinical approval of this device. As the realistic approach of more potent cytokine modulation, double PMMA-CHDF, in which 2 series of PMMA-CHDF was simultaneously performed, and PMMA-CHDF using a large sized PMMA dialyzer, in which membrane area is double of conventional hemofilter, were evaluated and their efficacy was confirmed clinically. Therefore, we conducted a prospective study to treat patients with hypercytokinemia based on the genetic analysis of cytokine related genes. This tailor-made therapy for hypercytokinemia based on genetic analysis of cytokine-related gene polymorphism has been approved by institute's ethics committee and now on going in our ICU.

  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (12 results)

  • [Journal Article] Blood purification for hypercytokinemia.2006

    • Author(s)
      Nakada T, Hirasawa H, Oda S, et al.
    • Journal Title

      Transfus Apher Sci 35

      Pages: 253-264

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Blood purification for hypercytokinemia.2006

    • Author(s)
      Taka-aki Nakada, Hiroyuki Hirasawa, Shigeto Oda, Hidetoshi Shiga, Ken-ichi Matsuda
    • Journal Title

      Transfus Apher Sci 35

      Pages: 253-264

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS) /sepsis.2005

    • Author(s)
      Shigeto Oda, Hiroyuki Hirasawa, Hidetoshi Shiga, et al.
    • Journal Title

      Cytokine 29

      Pages: 169-175

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients.2005

    • Author(s)
      Nakada T, Hirasawa H, Oda S, et al.
    • Journal Title

      J Surg Res 129

      Pages: 322-328

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cytokine-related genotypic differences in peak interleukin-6 blood levels of patients with SIRS and septic complications.2005

    • Author(s)
      Watanabe E, Hirasawa H, Oda S, et al.
    • Journal Title

      T Trauma 59

      Pages: 1181-1190

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sequential measurement of IL-6 blood levels in patients with systemic inflammatory response syndrome (SIRS)/sepsis.2005

    • Author(s)
      Shigeto Oda, Hiroyuki Hirasawa, Hidetoshi Shiga, Kazuya Nakanishi, Ken-ichi Matsuda, Masataka Nakamura
    • Journal Title

      Cytokine 29

      Pages: 169-175

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients.2005

    • Author(s)
      Taka-aki Nakada, Hiroyuki Hirasawa, Shigeto Oda, Hidetoshi Shiga, Ken-ichi Matsuda, Masataka Nakamura, Eizo Watanabe, Ryuzo Abe, Masahiko Hatano, Takeshi Tokuhisa
    • Journal Title

      J Surg Res 129

      Pages: 322-328

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cytokine-related genotypic differences in peak interleukin-6 blood levels of patients with SIRS and septic complications.2005

    • Author(s)
      Eizo Watanabe, Hiroyuki Hirasawa, Shigeto Oda, Hidetoshi Shiga, Kenichi Matsuda, Masataka Nakamura, Eizo Watanabe, Ryuzo Abe, Takaaki Nakada
    • Journal Title

      J Trauma 59

      Pages: 1181-1190

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] 敗血症と遺伝子多型2004

    • Author(s)
      渡邉栄三, 平澤博之, 織田成人, 中田孝明
    • Journal Title

      侵襲と免疫 13

      Pages: 22-29

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Cytokine adsorptive property of various adsorbents in immunoadsorption columns and a newly developed adsorbent : An in vitro study.2004

    • Author(s)
      Oda S, Hirasawa H, Shiga H, et al.
    • Journal Title

      Blood Purif 22

      Pages: 530-553

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Sepsis and cytokine-related gene polymorphism.2004

    • Author(s)
      Eizo Watanabe, Hiroyuki Hirasawa, Shigeto Oda, Taka-aki Nakada
    • Journal Title

      Surgical Trauma and Immunological Responses 13

      Pages: 22-29

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Cytokine adsorptive property of various adsorbents in immunoadsorption columns and a newly developed adsorbent : An in vitro study.2004

    • Author(s)
      Shigeto Oda, Hiroyuki Hirasawa, Hidetoshi Shiga, Kazuya Nakanishi, Ken-ichi Matsuda, Masataka Nakamura, Hiroyuki Ikeda, Masamune Sakai
    • Journal Title

      Blood Purif 22

      Pages: 530-536

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2008-05-27  

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