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

Mechanisms of endotoxin shock : Establishment of a new endotoxin shock model

Research Project

Project/Area Number 03670220
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field 細菌学
Research InstitutionIwate Medical University

Principal Investigator

INADA Katsuya  Iwate Medical University,School of Medicine Lecturer, 医学部, 講師 (80048446)

Co-Investigator(Kenkyū-buntansha) ENDO Shigeatsu  Iwate Medical University, School of Medicine Lecturer, 医学部, 講師 (30160394)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
KeywordsEndotoxin / Septic shock model / Lethality / Hypotension / Nitric oxide / Tumor necrosis factor-alpha / Interleukin-2 / Mouse / エンドトキシンショック / 動物モデル / 腫瘍壊死因子 / インタ-ロイキン2 / ポリミキシンB
Research Abstract

Cytokines and chemical mediators produced by endotoxin are thought to be the cause of endotoxin shock. Recently we investigated plasma cytokine and endotoxin levels in septic shock patients, and have found two types of septic shock, e.g, endotoxin + TNF-alpha + IL-2 type and IL-1beta and IL-6 type. In the former type of shock, two cytokines with extremely high levels were already present several days before the onset and shock was associated with sudden endotoxemia. However, only endotoxemia without previous elevation of cytokine levels did not induce shock. These are different from the previous concept as mentioned above, and the roles of these cytokines as to enhancement of endotoxin sensitivity were suggested. The purpose of this study is to confirm the roles of TNF-alpha and IL-2 for the induction of lethality by sublethal dose of endotoxin.
Results were as follows : 1) Sub-lethal dose of endotoxin and recombinant human (rh)TNF-alpha were synergistically induced lethality and hypote … More nsion in mice. 2) Recombinant human (rh)IL-2 alone did not show lethality in mice but shortened the interval from the injection to death by endotoxin and rhTNF-alpha. 3) The lethality induced by endotoxin, rhTNF-alpha and IL-2 was inhibited by polymyxin B injected 30 min before or soon after the mixture. 4) The lethality induced by high dose of endotoxin alone was inhibited by PAF antagonist or protease inhibitor, but the lethality by endotoxin. rhTNF-alpha and IL-2 was not. 5) IL-2 did not induce hypotension and had no effect on hypotension by endotoxin and rhTNF-alpha during early 180 min after the injection (we did not observed later changes). 6) Recombinant mouse (rm)TNF-alpha also had synergistic effect with endotoxin in lethality and hypotension. 7) Endotoxin induced the production of nitric oxide(NO) which accounts for the biological properties of endothelium-derived relaxing factor (EDRF) ; hypotension inducer. 8) rmTNF-alpha,but not rhTNF-alpha synergistically enhanced the NO production by endotoxin. 9) IL-2 in higher doses synergistically enhanced the NO production by endotoxin.
These results indicate that endotoxin and TNF-alpha induce hypotension and lethality. as previously reported by other authors, and IL-2 synergistically enhanced the lethality by endotoxin and TNF-alpha. However, IL-2 did not enhanced the hypotension in early period induced by endotoxin and TNF-alpha.
Thus, these results suggest that IL-2 involves in the pathogenesis of endotoxin shock in human. Less

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (5 results)

All Other

All Publications (5 results)

  • [Publications] K.INADA: "MODIFICATION OF ENDOTOXIN ACTIVITIES BY TNF-α AND IL-2." CIRCULATORY SHOCK.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.Inada, S.Endo, N.Yamashita, M.Suzuki and M.Yoshida: "Modification of endotoxin activities by TNF-alpha and IL-2"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] K.INADA: "MODIFICATION OF ENDOTOXIN ACTIVITES BY TNF-αAND IL-2." CIRCULATORY SHOCK.

    • Related Report
      1992 Annual Research Report
  • [Publications] 稲田 捷也: "エンドトキシンショック発現の機作:臨床的基礎的検討" 第38回毒素シンポジウム記録集. 132-135 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 稲田 捷也: "エンドトキシン、iーhTNF_2およびiーhILー2を用いたマウスエンドトキシンショックモデルの作成" 第4回エンドトキシンシンポジウム記録集. (1992)

    • Related Report
      1991 Annual Research Report

URL: 

Published: 1992-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi