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，其特征是子宫外子宫内膜样组织的存在和生长。子宫内膜异位症的发病机制及其与不孕症的关系存在争议。子宫内膜异位症患者腹腔液中含有大量激活的巨噬细胞，可分泌多种细胞因子，包括白介素6、白介素8和肿瘤坏死因子α。本研究旨在探讨IL-6、IL-8、肿瘤坏死因子α与内异症进展及不孕症的关系。子宫内膜异位症患者腹腔液中IL-6、IL-8、肿瘤坏死因子α水平明显高于非内异症患者。活动性子宫内膜异位症患者血清中这些细胞因子的浓度随着活动性病变的大小和数目的增加而升高。IL-6受体、糖蛋白130、IL-8受体和肿瘤坏死因子α受体在子宫内膜和子宫内膜…中均有表达肿瘤坏死因子-α以剂量依赖方式增加异位内膜细胞IL-6信使RNA和蛋白的表达。IL-6的加入抑制了小鼠1-细胞胚胎体外发育至囊胚。IL-6和可溶性IL-6受体的加入均可降低精子活动率。提示IL-6可能与子宫内膜异位症所致不孕症有关，IL-6对增生期子宫内膜间质细胞的生长无影响。相反，IL-6的加入显著抑制了分泌期组织中的基质细胞。而子宫内膜异位组织的间质细胞对IL-6有抵抗力，无抑制反应。IL-8可显著增加子宫内膜异位症间质细胞的数量和DNA合成，并呈剂量依赖关系。肿瘤坏死因子-α以剂量依赖方式诱导异位内膜基质细胞IL-8基因和蛋白表达。加入肿瘤坏死因子α可促进异位内膜基质细胞的增殖，而加入抗IL-8抗体可阻断肿瘤坏死因子α的刺激作用。结论：IL-6、IL-8和肿瘤坏死因子α可能参与了子宫内膜异位症和子宫内膜异位症相关不孕症的发病机制。较少

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