THE ROLE OF SUBCLINICAL INFECTION AND CYTOKINES IN PRETERM PARTURITION

早产是全世界围产儿死亡和发病率的主要原因。围产期研究分会将早产定义为一种综合征，并确定至少25%的早产是由患有亚临床宫内感染的妇女所生。此外，我们提供了许多早产儿在出生前就是危重疾病的证据，并提出在宫内感染的背景下早产的开始具有生存价值。本项目的目标是了解早产和分娩的病理生理学，今年我们研究的重点是确定促炎细胞因子及其受体和基质金属蛋白酶在足月和早产中的作用。研究结果如下：1)胎膜中性粒细胞胶原酶在胎膜早破、宫内感染或早产患者体内升高，中性粒细胞胶原酶是一种降解胎膜中胶原等细胞外基质成分的酶。2)宫内感染患者羊水中基质降解酶Matrilysin显著升高，而分娩或胎膜破裂患者羊水中Matrilysin无明显变化。这种酶可以激活天然抗菌肽(阿尔法防御素)，这是以前被证明在下生殖道表达的。3)早产妇女羊水中肿瘤坏死因子α可溶性受体增加，但足月正常分娩妇女羊水中肿瘤坏死因子α可溶性受体不增加。这些数据表明，早产不是简单的在胎儿成熟(足月)之前发生的分娩，而是一种具有不同病理生理特征的病理状态。4)有证据表明，新型趋化因子RANTES参与了宿主对宫内感染和分娩的反应。

Premature birth is the leading cause of perinatal mortality and morbidity worldwide. The Perinatology Research Branch has defined preterm labor as a syndrome and determined that at least 25% of all preterm births are born to women with sub-clinical intrauterine infection. Moreover, we have provided evidence that many premature neonates are critically ill before birth and proposed that the onset of premature labor has survival value in the context of intrauterine infection. The goal of this project is to understand the pathophysiology of premature labor and delivery and the focus of our research this year is to determine the role of pro-inflammatory cytokines, their receptors and matrix metalloproteinases in term and preterm labor. Our work resulted in the following findings:1) Neutrophil collagenase, an enzyme capable of degrading collagen and other components of extracellular matrix of the fetal membranes, is elevated in patients who have preterm premature rupture of membranes, intrauterine infection or premature labor. 2) Matrilysin, a matrix degrading enzyme implicated in the host defense against infection, is dramatically elevated in the amniotic fluid of patients with intrauterine infection but not in patients with labor or rupture of membranes. The enzyme may activate natural antimicrobial peptides (alpha defensins), which has been previously demonstrated to be expressed in the lower genital tract.3) Tumor necrosis factor alpha soluble receptors are increased in the amniotic fluid of women in preterm labor but not in those with normal labor at term. These data suggest that premature labor is not simply labor occurring before fetal maturity (term), but rather a pathologic condition with distinct pathophysiology.4) Evidence that the novel chemokine, RANTES, participates in the host response to intrauterine infection and parturition.