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细胞因子肿瘤坏死因子和白细胞介素-6在小鼠实验性胆道梗阻中的作用

Cytokines tumor necrosis factor and interleukin-6 in experimental biliary obstruction in mice.

作者信息

Bemelmans M H, Gouma D J, Greve J W, Buurman W A

机构信息

Department of Surgery, University of Limburg, Maastricht, The Netherlands.

出版信息

Hepatology. 1992 Jun;15(6):1132-6. doi: 10.1002/hep.1840150626.

DOI:10.1002/hep.1840150626
PMID:1592352
Abstract

The putative role of the cytokines interleukin-6 and tumor necrosis factor in the pathophysiology of the complications and mortality after surgery in jaundiced patients was studied in a murine model. Cytokine serum levels were determined in mice with experimental biliary obstruction. As an indicator of the activation status of macrophages, cytokine release by mononuclear phagocytes obtained from such mice was assessed. Following surgery, interleukin-6 levels increased to 2 to 3 ng/ml after 3 to 4 hr, but declined rapidly afterward to levels of 60 pg/ml after 10 days. After 12 days, substantial interleukin-6 levels were observed in jaundiced mice (100 pg/ml), whereas levels in sham mice further decreased (p less than 0.001). The cytokine tumor necrosis factor was frequently present in the serum of jaundiced mice. After 22 days, when killed, all jaundiced mice showed significant tumor necrosis factor levels (p less than 0.001). This was in contrast to sham mice in which tumor necrosis factor was never detected. The presence of an activated state of macrophages in jaundiced mice was concluded from the observed high spontaneous cytokine release and significantly higher release after stimulation (p less than 0.05). The presence of circulating cytokines was discussed in the context of the postoperative complications observed in jaundiced patients.

摘要

在一个小鼠模型中研究了细胞因子白细胞介素-6和肿瘤坏死因子在黄疸患者手术后并发症和死亡率的病理生理学中的假定作用。测定了实验性胆道梗阻小鼠的细胞因子血清水平。作为巨噬细胞活化状态的指标,评估了从此类小鼠获得的单核吞噬细胞释放的细胞因子。手术后,白细胞介素-6水平在3至4小时后升至2至3 ng/ml,但随后迅速下降,10天后降至60 pg/ml。12天后,黄疸小鼠中观察到大量白细胞介素-6水平(100 pg/ml),而假手术小鼠中的水平进一步降低(p<0.001)。细胞因子肿瘤坏死因子经常出现在黄疸小鼠的血清中。22天后处死时,所有黄疸小鼠均显示出显著的肿瘤坏死因子水平(p<0.001)。这与从未检测到肿瘤坏死因子的假手术小鼠形成对比。从观察到的高自发细胞因子释放以及刺激后显著更高的释放(p<0.05)得出黄疸小鼠中存在巨噬细胞活化状态的结论。在黄疸患者观察到的术后并发症的背景下讨论了循环细胞因子的存在。

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