Effects of cytokines on the pathogenesis of endometriosis and infertility associated with endometriosis

子宫内膜异位症发生在10%的育龄妇女中，其特征是子宫外存在和生长子宫内膜样组织。子宫内膜异位症的发病机制及其与不孕的关系是有争议的。子宫内膜异位症患者的腹膜液中含有大量分泌多种细胞因子的活化巨噬细胞，包括白细胞介素(IL)-6、IL-8和肿瘤坏死因子-α (tnf -α)。本研究旨在探讨IL-6、IL-8和TNFα是否与本病的进展和不孕有关。子宫内膜异位症患者腹膜液中IL-6、IL-8和TNFα水平明显高于无子宫内膜异位症患者。活动性子宫内膜异位症患者体内这些细胞因子的浓度随着活动性病变的大小和数量的增加而增加。IL-6受体、糖蛋白130、IL-8受体和tnf - α受体在子宫内膜和子宫内膜间质细胞中均有表达。肿瘤坏死因子-α增加子宫内膜异位症细胞中IL-6信使RNA和蛋白的表达呈剂量依赖性。IL-6的加入抑制了小鼠1细胞胚向囊胚的发育。同时添加IL-6和可溶性IL-6受体可降低精子的活动百分率。这些结果提示IL-6可能与子宫内膜异位症相关的不孕有关。白细胞介素-6对增殖期子宫内膜间质细胞的生长无影响。相反，IL-6的加入诱导了组织中秘书期基质细胞的显著抑制。另一方面，子宫内膜异位症组织间质细胞对IL-6有抗性，无抑制反应。白细胞介素-8显著增加子宫内膜异位症间质细胞的细胞数量和DNA合成，并呈剂量依赖性。肿瘤坏死因子-α诱导子宫内膜异位症间质细胞IL-8基因和蛋白表达呈剂量依赖性。TNF α的加入促进了子宫内膜异位症间质细胞的增殖，并通过添加抗il -8抗体来消除TNF α的刺激作用。这些细胞因子可能与疾病的进展有关。综上所述，IL-6、IL-8和TNF α可能参与了子宫内膜异位症及子宫内膜异位症相关不孕的发病机制。少

Endometriosis, which occurs in 10% of reproductive aged women, is characterized by the presence and growth of endometrial-like tissue outside the uterus. The pathogenesis of endometriosis and its link to infertility is controversial. Peritoneal fluid in women with endometriosis contains an increased number of activated macrophages that secrete a variety of cytokines, including interleukin (IL)-6, IL-8 and tumor necrosis factor-α (TNFα). The purpose of this study is to investigate whether IL-6, IL-8 and TNFα are related to progress and infertility of this disease.Peritoneal fluid levels of IL-6, IL-8 and TNFα were significantly higher in patients with endometriosis compared with patients without endometriosis. The concentrations of these cytokines in patients with active endometriosis increased as the size and number of active lesions increased. Expressions of transcripts of IL-6 receptor, glycoprotein 130, IL-8 receptor and TNFα receptor were observed in both endometrial and endometrio … More tic stromal cells.Tumor necrosis factor-α increased the expression of IL-6 messenger RNA and protein in endometriotic cells in a dose-dependent manner. The addition of IL-6 inhibited the development of mouse 1-cell embryo to blastocyst in vitro. The percentage of motile spermatoza decreased by the addition of both IL-6 and soluble IL-6 receptor. These results suggested that IL-6 may relate to the infertility associated with endometriosis.Interleukin-6 had no effect on the growth of stromal cells in endometrial tissue from the proliferative phase. In contrast, the addition of IL-6 induced significant inhibition of stromal cells in tissue from the secretary phase. On the other hand, stromal cells of endometriotic tissues were resistant to IL-6, showing no inhibitory response. Interleukin-8 significantly increased the number of cells and DNA synthesis in the endometriotic stromal cells in a dose-dependent manner. Tumor necrosis factor-α induced the gene and protein expression of IL-8 in endometriotic stromal cells in a dose-dependent fashion. The addition of TNF α promoted the proliferation of the endometriotic stromal cells, and the stimulatory effects of TNF α were abolished by the adding anti-IL-8 antibody. These cytokines may associate with the progression of the disease.In conclusion, IL-6, IL-8 and TNF α may contribute to the pathogenesis of endometriosis and infertility associated with endometriosis. Less