Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U. S. Department of Health and Human Services, Detroit, MI, USA.
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
Am J Reprod Immunol. 2019 Nov;82(5):e13171. doi: 10.1111/aji.13171. Epub 2019 Sep 3.
Preterm birth is commonly preceded by preterm labor, a syndrome that is causally linked to both intra-amniotic infection and intra-amniotic inflammation. However, the stereotypical cellular immune responses in these two clinical conditions are poorly understood.
Amniotic fluid samples (n = 26) were collected from women diagnosed with preterm labor and intra-amniotic infection (amniotic fluid IL-6 concentrations ≥2.6 ng/mL and culturable microorganisms, n = 10) or intra-amniotic inflammation (amniotic fluid IL-6 concentrations ≥2.6 ng/mL without culturable microorganisms, n = 16). Flow cytometry was performed to evaluate the phenotype and number of amniotic fluid leukocytes. Amniotic fluid concentrations of classical pro-inflammatory cytokines, type 1 and type 2 cytokines, and T-cell chemokines were determined using immunoassays.
Women with spontaneous preterm labor and intra-amniotic infection had (a) a greater number of total leukocytes, including neutrophils and monocytes/macrophages, in amniotic fluid; (b) a higher number of total T cells and CD4 T cells, but not CD8 T cells or B cells, in amniotic fluid; and (c) increased amniotic fluid concentrations of IL-6, IL-1β, and IL-10, compared to those with intra-amniotic inflammation. However, no differences in amniotic fluid concentrations of T-cell cytokines and chemokines were observed between these two clinical conditions.
The cellular immune responses observed in women with preterm labor and intra-amniotic infection are more severe than in those with intra-amniotic inflammation, and neutrophils, monocytes/macrophages, and CD4 T cells are the main immune cells responding to microorganisms that invade the amniotic cavity. These findings provide insights into the intra-amniotic immune mechanisms underlying the human syndrome of preterm labor.
早产通常先于早产临产，早产临产是一种综合征，与羊膜内感染和羊膜内炎症均有关。然而，这两种临床情况下的典型细胞免疫反应还知之甚少。
从诊断为早产临产且羊膜内感染（羊膜液白细胞介素 6 浓度≥2.6ng/ml 且可培养微生物，n=10）或羊膜内炎症（羊膜液白细胞介素 6 浓度≥2.6ng/ml 但无可培养微生物，n=16）的女性中采集羊水样本（n=26）。采用流式细胞术评估羊水白细胞的表型和数量。采用免疫分析法测定羊水内经典促炎细胞因子、1 型和 2 型细胞因子及 T 细胞趋化因子的浓度。
自发性早产临产且羊膜内感染的女性存在以下特征：（a）羊水中总白细胞（包括中性粒细胞和单核细胞/巨噬细胞）数量较多；（b）羊水中总 T 细胞和 CD4 T 细胞数量较多，但 CD8 T 细胞和 B 细胞数量无差异；（c）羊水中白细胞介素 6、白细胞介素 1β 和白细胞介素 10 浓度较高。然而，这两种临床情况下的羊水 T 细胞细胞因子和趋化因子浓度无差异。
早产临产且羊膜内感染女性的细胞免疫反应比羊膜内炎症女性更严重，中性粒细胞、单核细胞/巨噬细胞和 CD4 T 细胞是对侵入羊膜腔的微生物作出反应的主要免疫细胞。这些发现为人类早产临产综合征的羊膜内免疫机制提供了新的见解。
