Department of Woman and Child Health, Karolinska Institute, FRH-lab C4:U1, KBH, 171 76 Stockholm, Sweden.
J Reprod Immunol. 2010 Mar;84(2):176-85. doi: 10.1016/j.jri.2009.12.004. Epub 2010 Jan 21.
Cervical ripening is necessary for successful delivery. Since cytokines are believed to be involved in this process, the aim of this study was to investigate possible changes in the mRNA and protein expression of pro-inflammatory cytokines (interleukin (IL)-1alpha, IL-1beta, IL-12, IL-18) and anti-inflammatory cytokines (IL-4, IL-10, IL-13) in the human cervix during pregnancy, term and preterm labor. Cervical biopsies were taken from 59 women: 21 at preterm labor, 24 at term labor, 10 at term not in labor and 4 from non-pregnant women. mRNA was analyzed with real-time RT-PCR and protein expression and/or secretion with immunohistochemistry and ELISA. There was an upregulation of mRNA for IL-10, IL-13, IL-1alpha and IL-1beta in the laboring groups, while mRNA for IL-12 and IL-18 was downregulated. IL-4 mRNA was detected more frequently, while IL-12 mRNA expression was lower, in the preterm labor group than in the term labor group. The protein levels of IL-4 and IL-12 were lower and IL-18 tended to be higher in the labor groups, while IL-10 protein levels were unaffected by labor. IL-4 protein levels were significantly higher in the preterm subgroup with bacterial infection than in the non-infected group. IL-10 had higher expression in squamous epithelium at preterm labor than at term. In conclusion, the major changes in pro-inflammatory and anti-inflammatory cytokine mRNA and protein expression in cervix occur during the labor process irrespective of the length of gestation. Our results indicate that dysregulation of anti-inflammatory cytokines in the human cervix could be involved in the pathogenesis of preterm labor.
宫颈成熟是成功分娩的必要条件。由于细胞因子被认为参与了这个过程,本研究旨在探讨妊娠、足月和早产时人宫颈中促炎细胞因子(白细胞介素 (IL)-1alpha、IL-1beta、IL-12、IL-18)和抗炎细胞因子(IL-4、IL-10、IL-13)的 mRNA 和蛋白表达可能发生的变化。从 59 名妇女中采集宫颈活检:21 名早产,24 名足月分娩,10 名足月未分娩,4 名非孕妇。采用实时 RT-PCR 分析 mRNA,免疫组织化学和 ELISA 分析蛋白表达和/或分泌。在分娩组中,IL-10、IL-13、IL-1alpha 和 IL-1beta 的 mRNA 上调,而 IL-12 和 IL-18 的 mRNA 下调。与足月分娩组相比,早产组 IL-4 mRNA 的检出率更高,而 IL-12 mRNA 的表达水平更低。IL-4 和 IL-12 的蛋白水平在分娩组中较低,IL-18 则趋于升高,而 IL-10 蛋白水平不受分娩影响。在有细菌感染的早产亚组中,IL-4 蛋白水平明显高于无感染组。IL-10 在早产时的宫颈鳞状上皮中的表达高于足月时。总之,促炎和抗炎细胞因子的 mRNA 和蛋白表达的主要变化发生在分娩过程中,与妊娠时间长短无关。我们的结果表明,人宫颈中抗炎细胞因子的失调可能与早产的发病机制有关。