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白细胞介素-18在子宫内膜异位症发病机制中的作用。

Role of IL-18 in pathogenesis of endometriosis.

作者信息

Oku H, Tsuji Y, Kashiwamura S-I, Adachi S, Kubota A, Okamura H, Koyama K

机构信息

Department of Obstetrics and Gynecology, Institute for Advanced Medical Sciences, Japan.

出版信息

Hum Reprod. 2004 Mar;19(3):709-14. doi: 10.1093/humrep/deh108. Epub 2004 Jan 29.

DOI:10.1093/humrep/deh108
PMID:14998974
Abstract

BACKGROUND

Endometriosis is a complex disease associated with a wide range of immune responses, including pain, adhesion, exudation of peritoneal fluid, elevation of cytokine levels and generation of autoantibodies. Interleukin (IL)-18 is a strong pleiotropic cytokine known to be involved in various immune diseases. The aim of this study is to elucidate the role of IL-18 in the pathogenesis of endometriosis.

METHODS

IL-18 and IL-1beta concentrations were measured in the peritoneal fluid and sera of 39 endometriosis patients and 15 control women. Expression of IL-18 and IL-18 receptor alpha-chain (IL-18Ralpha) was analysed in endometriotic tissues immunohistochemically. The effects of IL-18 on cyclooxygenase (COX)-II gene expression were analysed in peritoneal fluid monocytes and endometriotic cells of endometriosis patients.

RESULTS

IL-18 concentrations in the peritoneal fluid of endometriosis patients averaged 592.57 +/- 108.27 pg/ml, significantly higher than 260.50 +/- 55.88 pg/ml in non-endometriotic samples. IL-18 concentrations in the serum did not differ significantly between endometriosis and control patients. Similarly, no significant differences were observed in IL-1beta concentrations in either the peritoneal fluid or the serum. IL-18 and IL-18Ralpha were expressed in endometriotic tissues. IL-18Ralpha expression was also observed in cells infiltrating into the inflammatory area of the endometriosis patients. COX-II was induced in peritoneal fluid monocytes and in endometriotic cells in response to IL-18 stimulation.

CONCLUSIONS

The elevation of IL-18 in the peritoneal fluid of endometriosis patients and the induction of COX-II in peritoneal monocytes by IL-18 suggest that IL-18 plays a pathogenic role in endometriosis.

摘要

背景

子宫内膜异位症是一种复杂的疾病,与多种免疫反应相关,包括疼痛、粘连、腹腔液渗出、细胞因子水平升高以及自身抗体的产生。白细胞介素(IL)-18是一种强大的多效性细胞因子,已知参与多种免疫疾病。本研究的目的是阐明IL-18在子宫内膜异位症发病机制中的作用。

方法

检测39例子宫内膜异位症患者和15例对照女性的腹腔液和血清中IL-18和IL-1β的浓度。采用免疫组织化学方法分析子宫内膜异位症组织中IL-18和IL-18受体α链(IL-18Rα)的表达。分析IL-18对子宫内膜异位症患者腹腔液单核细胞和异位内膜细胞中环氧合酶(COX)-II基因表达的影响。

结果

子宫内膜异位症患者腹腔液中IL-18浓度平均为592.57±108.27 pg/ml,显著高于非子宫内膜异位症样本中的260.50±55.88 pg/ml。子宫内膜异位症患者与对照患者血清中IL-18浓度无显著差异。同样,腹腔液或血清中IL-1β浓度也未观察到显著差异。IL-18和IL-18Rα在子宫内膜异位症组织中表达。在浸润到子宫内膜异位症患者炎症区域的细胞中也观察到IL-18Rα表达。IL-18刺激后,腹腔液单核细胞和异位内膜细胞中COX-II被诱导。

结论

子宫内膜异位症患者腹腔液中IL-18升高以及IL-18诱导腹腔单核细胞中COX-II表明IL-18在子宫内膜异位症中起致病作用。

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