Shynlova Oksana, Dorogin Anna, Li Yunqing, Lye Stephen
Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Department of Obstetrics & Gynecology, University of Toronto, Toronto, ON, Canada.
J Cell Mol Med. 2014 Sep;18(9):1816-29. doi: 10.1111/jcmm.12307. Epub 2014 Jun 4.
Preterm birth (PTB) is the single most important cause of perinatal and infant mortality worldwide. Maternal infection can result in PTB. We investigated the ability of a Broad Spectrum Chemokine Inhibitor (BSCI) to prevent infection-induced PTB in mice. PTB was initiated in pregnant mice by intraperitoneal injection of lipopolysaccharide (LPS; 50 μg). Half the mice received BSCI (10 mg/kg) 24 hrs prior to and immediately before LPS administration. The impact of LPS alone or LPS plus BSCI was assessed on (i) injection-to-delivery interval, foetal survival rate, placental and neonates' weight; (ii) amniotic fluid and maternal plasma cytokine levels (by Luminex assay); foetal and maternal tissue cytokine gene expression levels (by Real-Time RT-PCR); (iii) immune cells infiltration into the uterine tissue (by stereological immunohistochemistry). Pre-treatment with BSCI (i) decreased LPS-induced PTB (64% versus 100%, P < 0.05); (ii) significantly attenuated cytokine/chemokine expression in maternal tissues (plasma, liver, myometrium, decidua); (iii) significantly decreased neutrophil infiltration in the mouse myometrium. BSCI-treated mice in which PTB was delayed till term had live foetuses with normal placental and foetal weight. BSCI represents a promising new class of therapeutics for PTB. In a mouse model of preterm labour, BCSI suppresses systemic inflammation in maternal tissues which resulted in the reduced incidence of LPS-mediated PTB. These data provide support for efforts to target inflammatory responses as a means of preventing PTB.
早产是全球围产期和婴儿死亡的最重要单一原因。母体感染可导致早产。我们研究了一种广谱趋化因子抑制剂（BSCI）预防小鼠感染诱导早产的能力。通过腹腔注射脂多糖（LPS；50μg）在怀孕小鼠中引发早产。一半小鼠在LPS给药前24小时和给药前立即接受BSCI（10mg/kg）。评估单独LPS或LPS加BSCI对以下方面的影响：（i）注射至分娩间隔、胎儿存活率、胎盘和新生儿体重；（ii）羊水和母体血浆细胞因子水平（通过Luminex测定法）；胎儿和母体组织细胞因子基因表达水平（通过实时RT-PCR）；（iii）免疫细胞浸润到子宫组织中（通过体视学免疫组织化学）。用BSCI预处理（i）降低了LPS诱导的早产（64%对100%，P<0.05）；（ii）显著减弱母体组织（血浆、肝脏、子宫肌层、蜕膜）中细胞因子/趋化因子的表达；（iii）显著减少小鼠子宫肌层中的中性粒细胞浸润。BSCI治疗的小鼠中早产延迟至足月，胎儿存活，胎盘和胎儿体重正常。BSCI代表了一种有前途的新型早产治疗药物。在早产小鼠模型中，BCSI抑制母体组织中的全身炎症，这导致LPS介导的早产发生率降低。这些数据为将炎症反应作为预防早产的一种手段的努力提供了支持。
