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Hypercytokinemia a underlies the morbid condition of sepsis.

高细胞因子血症是败血症病态的基础。

基本信息

批准号：
15390547
负责人：
ENDO Shigeatsu
金额：
$ 7.1万
依托单位：
Iwate Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In sepsis, inflammatory cytokines are produced as a local or systemic reaction, and cytokines produced locally act on distant organs. Cytokines are produced in abnormal quantities in the presence of sepsis. Cytokine production is controlled positively and negatively, and abnormal production is usually suppressed. However, when cytokines are produced in abnormal quantities as a result of a disorder of control, irreversible morbid conditions including ARDS, DIC and sepsis are induced. The most severe morbid condition is septic shock. It often progresses to multiple organ failure, frequently leading to a fatal course. In this process, phospholipase A2, eicosanoid, nitrogen monoxide, endothelin-1, thrombomodulin, neutrophil elastase, adhesion molecules, and so on are produced in response to stimulation with cytokines. They induce cytotoxicity and tissue disorder directly or indirectly, thereby leading to complicated morbid conditions. It was confirmed that neutrophils play an important role in the secondary systemic response to sepsis. The observation indicates that activation of neutrophils fixes the course of systemic sepsis to establish conditions for the development of septic shock and multiple organ failure. Our future research tasks include phenomenological elucidation of details of the general secondary systemic response, acquisition of fundamental knowledge contributing to treatment of septic shock and multiple organ failure, and construction of a theory of infection control on the basis of changes in bio-reactivity.

在脓毒症中，炎症细胞因子是作为局部或全身反应产生的，而局部产生的细胞因子作用于远处的器官。在出现脓毒症时，细胞因子的产生是异常的。细胞因子的产生受到正负两方面的控制，异常产生通常被抑制。然而，当细胞因子由于控制障碍而产生异常数量时，就会导致不可逆的病态情况，包括ARDS、DIC和败血症。最严重的病态是感染性休克。它通常进展为多器官衰竭，经常导致致命的病程。在这个过程中，磷脂酶A2、二十烷类化合物、一氧化氮、内皮素-1、血栓调节蛋白、中性粒细胞弹性蛋白酶、黏附分子等在细胞因子的刺激下产生。它们直接或间接地引起细胞毒性和组织紊乱，从而导致复杂的病态情况。已有研究证实，中性粒细胞在脓毒症继发性全身反应中起重要作用。观察表明，中性粒细胞的激活固定了全身脓毒症的病程，为感染性休克和多器官衰竭的发展创造了条件。我们未来的研究任务包括从现象学的角度阐明一般继发性全身反应的细节，获取有助于感染性休克和多器官衰竭治疗的基础知识，以及根据生物反应性的变化构建感染控制理论。