THE ROLE OF SUBCLINICAL INFECTION AND CYTOKINES IN PRETERM PARTURITION

早产是全世界围产期死亡率和发病率的主要原因。 围产期研究分支将早产定义为一种综合征，并确定至少25%的早产儿是由亚临床宫内感染的妇女所生。 此外，我们提供的证据表明，许多早产儿在出生前就已病危，并提出在宫内感染的背景下，早产的发生具有生存价值。 该项目的目标是了解早产和分娩的病理生理学，我们今年的研究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。我们的工作导致了以下结果：1）Neutraline胶原酶，一种能够降解胶原和胎膜细胞外基质的其他成分的酶，在患有早产胎膜早破、宫内感染或早产的患者中升高。2)基质溶素是一种基质降解酶，参与宿主对感染的防御，在宫内感染患者的羊水中显著升高，但在分娩或胎膜破裂患者中则不升高。 这种酶可以激活天然的抗菌肽（α防御素），以前已经证明它在下生殖道中表达。3）肿瘤坏死因子α可溶性受体在早产妇女的羊水中增加，但在足月正常分娩的妇女中没有增加。 这些数据表明，早产不只是分娩发生在胎儿成熟（术语）之前，而是一种具有独特病理生理学的病理条件。4）证据表明，新的趋化因子，RANTES，参与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.