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Determination of cytokines involved in initiation of acute inflammation.

测定参与急性炎症引发的细胞因子。

基本信息

批准号：
07457060
负责人：
YOSHINAGA Masaru
金额：
$ 4.86万
依托单位：
Kumamoto University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457060/
关键词：
inflammation cytokine TNF IL-8 IL-1 IL-1ra TNFα IL-lβ IL-lra IL-1β IL-1ra

项目摘要

To know the cytokines involved in the development of inflammation. We developed a subtraction gene library of rabbit and detected several candidate cytokines which are specifically expressed during the course of inflammation, i.e.TNFalpha), IL-8, IL-1beta and IL-1ra. Then, we made recombinants and antibodies of these gene products and investigated the significance of these cytokines in the pathogenesis of LPS-induced acute inflammation in rabbits.We conclude the followings :1. TNFalpha and IL-8 were produced during the initial stage (within 2 hrs). The production of these cytokines were mutually independent, namely inhibition of one of these did not suppressed the production of the other. The production was not reduced by depletion of neutrophils. Immunostaining revealed that resident cells were positive for these two cytokines, but not neutrophils.2. IL-1beta was produced during a later stage (peaked at 6 hrs). Production of IL-1beta was induced by both TNFalpha and IL-8 ; namely, inhibition of the two cytokines resulted in reduced production of IL-1beta. Recombinant TNFalpha or IL-8 induced the strong production of IL-1beta.3. IL-1 ra was produced by infiltrated neutrophils and macrophages and suppressed by inhibition of TNFalpha and IL-8. Recombinant IL-1ra suppressed the infiltration of neutrophils. Inhibition of IL-1ra produced enhanced neutrophil infiltration and tissue destruction.4. Inhibition of TNFalpha or IL-8 resulted in a partial inhibition of neutrophil infiltration at an early stage (2 hrs) of inflammation, but not those in a later stage (9 hrs).5. Inhibition of IL-1 resulted in reduced neutrophil infiltration at the later stage of inflammation. Then, we reached a conclusion that both TNFalpha and IL-8 act as initiation of inflammation and IL-1beta play a role in the amplification of acute inflammation.

了解参与炎症发生发展的细胞因子。我们建立了一个兔差减基因文库，检测了几种在炎症过程中特异性表达的候选细胞因子，即TNF α、IL-8、IL-1 β和IL-1 ra。然后，我们制备了这些基因产物的重组体和抗体，并研究了这些细胞因子在LPS诱导的家兔急性炎症发病机制中的意义。TNF α和IL-8在初始阶段（2小时内）产生。这些细胞因子的产生是相互独立的，即抑制其中一种细胞因子并不抑制另一种细胞因子的产生。中性粒细胞的消耗不会减少生产。免疫组化结果显示，驻留细胞对这两种细胞因子呈阳性反应，而嗜酸性粒细胞不呈阳性反应. IL-1 β在后期产生（在6小时达到峰值）。TNF α和IL-8均可诱导IL-1 β的产生;即，抑制这两种细胞因子导致IL-1 β的产生减少。重组TNF α或IL-8诱导IL-1 β的强烈产生。IL-1 ra由浸润的中性粒细胞和巨噬细胞产生，并被TNF α和IL-8的抑制所抑制。重组IL-1 ra可抑制中性粒细胞的浸润。抑制IL-1 ra可增强中性粒细胞浸润和组织破坏. TNF α或IL-8的抑制导致在炎症的早期阶段（2小时）部分抑制中性粒细胞浸润，但在后期阶段（9小时）不抑制。抑制IL-1导致炎症后期中性粒细胞浸润减少。因此，我们得出结论，TNF α和IL-8均作为炎症的起始，而IL-1 β在急性炎症的放大中起作用。