Matsuzaki N
Department of Obstetrics and Gynecology, Osaka University Medical School.
Nihon Sanka Fujinka Gakkai Zasshi. 1994 Aug;46(8):697-706.
Recent analysis of a various kinds of cytokines revealed that the cytokines are actively involved in a number of important biological functions including immunological and endocrine functions. The present study investigated the unique cytokine-mediated immunological and endocrinological functions in the intra-uterine space during pregnancy. A human placenta which expresses paternal and maternal antigens was revealed to escape from maternal immune systems by releasing immunosuppressive cytokines derived from the placenta. Placental cytokines such as interleukin-6 (IL-6) activated IL-6-receptor-mediated signal transduction pathways to produce human chorionic gonadotropin (hCG). IL-1 and tumor necrosis factor-alpha (TNF-alpha) synergistically augmented IL-6 production to stimulate hCG production. However, transforming growth factor-beta (TGF-beta) suppressed these cytokine-mediated hCG production as well as IL-6 production. Thus, these placental cytokines, mainly derived from trophoblasts, cooperatively contributed to hCG production. IL-8 and monocyte chemotactic and activating factor (MCAF) activate host defense mechanism by activating neutrophils and monocytes as well as macrophages, respectively. IL-6 also activates immune responses and promote synthesis of acute-phase reactant proteins, contributing to augmentation of host defense mechanism in a different way from IL-8 and MCAF. Human placenta in the 3rd trimester actively produced these cytokines for potentiation of placental defense mechanism during pregnancy and in chorioamnionitis. A fetus in chorioamnionitis also produced these cytokines in utero for potentiation of fetal defense mechanism. Among these cytokines, IL-8 in a cord serum was a very sensitive and useful marker for clinical diagnosis of chorioamnionitis. Cord serum IL-6, in contrast, stimulated the synthesis of surfactant protein-A (SP-A) to promote fetal lung maturation and reduce the incidence of RDS. Collectively, the present study revealed the cytokine network in the placenta regulating maternal immune responses, placental endocrine functions, feto-maternal defense mechanism and fetal respiratory maturation.
近期对多种细胞因子的分析表明，这些细胞因子积极参与包括免疫和内分泌功能在内的许多重要生物学功能。本研究调查了妊娠期间子宫内独特的细胞因子介导的免疫和内分泌功能。研究发现，表达父源和母源抗原的人胎盘通过释放源自胎盘的免疫抑制细胞因子来逃避母体免疫系统。胎盘细胞因子如白细胞介素-6（IL-6）激活IL-6受体介导的信号转导途径以产生人绒毛膜促性腺激素（hCG）。白细胞介素-1（IL-1）和肿瘤坏死因子-α（TNF-α）协同增强IL-6的产生以刺激hCG的产生。然而，转化生长因子-β（TGF-β）抑制这些细胞因子介导的hCG产生以及IL-6的产生。因此，这些主要源自滋养层细胞的胎盘细胞因子共同促进了hCG的产生。白细胞介素-8（IL-8）和单核细胞趋化激活因子（MCAF）分别通过激活中性粒细胞、单核细胞以及巨噬细胞来激活宿主防御机制。IL-6也激活免疫反应并促进急性期反应蛋白的合成，以与IL-8和MCAF不同的方式促进宿主防御机制的增强。妊娠晚期的人胎盘积极产生这些细胞因子，以增强妊娠期间和绒毛膜羊膜炎时的胎盘防御机制。患有绒毛膜羊膜炎的胎儿也在子宫内产生这些细胞因子，以增强胎儿防御机制。在这些细胞因子中，脐带血清中的IL-8是绒毛膜羊膜炎临床诊断的非常敏感且有用的标志物。相比之下，脐带血清IL-6刺激表面活性蛋白-A（SP-A）的合成，以促进胎儿肺成熟并降低呼吸窘迫综合征（RDS）的发生率。总体而言，本研究揭示了胎盘中调节母体免疫反应、胎盘内分泌功能、母胎防御机制和胎儿呼吸成熟的细胞因子网络。
