| Project/Area Number |
04454233
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NARIUCHI Hideo Inst.of Med.Sci., The Univ.of Tokyo, Professor, 医科学研究所, 教授 (10012741)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMOTO Takayuki Inst.of Med.Sci., The Univ.of Tokyo, Research Associate, 医科学研究所, 助手 (80202406)
KATO Takuma Inst.of Med.Sci., The Univ.of Tokyo, Research Associate, 医科学研究所, 助手 (60224515)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1992: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Inflammation / Cytokine / Tumor necrosis factor / Interferon / T helper cell subset / 腫瘍壊死因子 / 内毒素 / 炎症反応 / インターロイセン1 |
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| Research Abstract |
The goal of this project is to elucidate the contribution of various cytokines in inflammatory reaction and to obtain basic findings for the application of the results to regulation of the reaction. In experiments in model system using bacterial endotoxin as a causative agent, tumor necrosis factor (TNF) and interleukin 1(IL-1) were revealed to play an essential role as the causative cytokines of the inflammatory reaction by using the combinations of these cytokines and antibodies. We are now carring out experiments to study the mutual relationship of these cytokines, kinetically and functionally, however, our preliminary results indicated that TNF plays a central role in inducing the reaction. The production of TNF was shown to be augmented by interferon gamma (IFN) produced by a subpopulation of Th cells, Th1, in the hepatitis model experiments of murine malaria. In the experiments IFN was demonstrated to cure mice from malaria on one hand and on the other hand enhance the inflammatory reaction in liver to cause fatal changes of hepatocytes, indicating that IFN is the important cytokine for the target of hepatitis treatment. IFN is known to be produced by Th1 cells. In other words, it is important for at least hepatitis which subset of T cells is activated by the infection. Our results strongly indicated that second signal determines the T cell subset to be activated, IL-12 for Th1 and IL-1 for Th2. These results indicate that cytokine cascade in inflammation starts from IL-12 to IFN and then to TNF.IL-1 produced by macrophages regulates the function of TNF.Our presents results indicate that IFN would be the major target for the regulation of the cascade.
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