Pulmonary and systemic inflammatory responses to intra-amniotic IL-1α in fetal sheep
Pulmonary and systemic inflammatory responses to intra-amniotic IL-1α in fetal sheep
复制标题
DOI：
10.1152/ajplung.00446.2010
复制
发表时间：
2011-09-01
影响因子：
4.9
通讯作者：
Jobe, Alan H.
中科院分区：
文献类型：
--
作者：
Kallapur, Suhas G.;Kramer, Boris W.;Jobe, Alan H.
卡拉普尔SG，克莱默BW，尼措斯I，皮洛JJ，柯林斯JJP，波格拉斯GR，纽纳姆JP，乔布AH。胎羊羊膜腔内白细胞介素 - 1α引发的肺部和全身炎症反应。《美国生理学杂志 - 肺细胞与分子生理学》301卷：L285 - L295，2011年。首次发表于2011年6月10日；doi:10.1152/ajplung.00446.2010。 - 临床和流行病学研究表明白细胞介素 - 1是围产期炎症的重要介质。我们验证了羊膜腔内白细胞介素 - 1α会诱发胎儿肺部和全身炎症反应这一假设。怀有单胎的绵羊接受羊膜腔内注射重组绵羊白细胞介素 - 1α（100微克），并分别在妊娠124 ± 1天的1天、3天或7天后分娩（每组n = 5 - 8）。另一组绵羊接受两次羊膜腔内白细胞介素 - 1α注射（每次剂量100微克）：分娩前7天和1天。白细胞介素 - 1α使支气管肺泡灌洗液中的单核细胞、中性粒细胞、淋巴细胞和白细胞介素 - 8蛋白显著增加。与对照单核细胞相比，体外脂多糖刺激时，从接触白细胞介素 - 1α的羔羊肺部分离出的炎症细胞中过氧化氢分泌增加。T淋巴细胞被募集到肺部。羊膜腔内白细胞介素 - 1α暴露1天后，肺中白细胞介素 - 1β、环氧化酶 - 1和环氧化酶 - 2的mRNA表达增加。羊膜腔内白细胞介素 - 1α暴露7天后肺容积增加，气腔形态的解剖学变化极小。接触白细胞介素 - 1α后，引流肺部和胃肠道的后纵隔淋巴结重量翻倍，诱导型一氧化氮合酶（NOSII）阳性细胞增加，淋巴结中Foxp3阳性的调节性T淋巴细胞减少。在血液中，白细胞介素 - 1α暴露后中性粒细胞计数和血浆触珠蛋白增加。与单次暴露相比，分娩前7天和1天两次暴露于羊膜腔内白细胞介素 - 1α产生了不同的影响（一些炎症标志物增加，但肺部细胞因子未增加）。白细胞介素 - 1α是胎儿炎症反应综合征的一种强效介质。
Kallapur SG, Kramer BW, Nitsos I, Pillow JJ, Collins JJP, Polglase GR, Newnham JP, Jobe AH. Pulmonary and systemic inflammatory responses to intra-amniotic IL-1 alpha in fetal sheep. Am J Physiol Lung Cell Mol Physiol 301: L285-L295, 2011. First published June 10, 2011; doi:10.1152/ajplung.00446.2010.-Clinical and epidemiological studies implicate IL-1 as an important mediator of perinatal inflammation. We tested the hypothesis that intra-amniotic IL-1 alpha would induce pulmonary and systemic fetal inflammatory responses. Sheep with singleton fetuses were given an intra-amniotic injection of recombinant sheep IL-1 alpha (100 mu g) and were delivered 1, 3, or 7 days later, at 124 +/- 1 days gestation (n = 5-8/group). A separate group of sheep were given two intra-amniotic IL-1 alpha injections (100 mu g dose each): 7 days and again 1 day prior to delivery. IL-1 alpha induced a robust increase in monocytes, neutrophils, lymphocytes, and IL-8 protein in bronchoalveolar lavage fluid. H2O2 secretion was increased in inflammatory cells isolated from lungs of IL-1 alpha-exposed lambs upon LPS challenge in vitro compared with control monocytes. T lymphocytes were recruited to the lung. IL-1 beta, cyclooxygenase-1, and cyclooxygenase-2 mRNA expression increased in the lung 1 day after intra-amniotic IL-1 alpha exposure. Lung volumes increased 7 days after intra-amniotic IL-1 alpha exposure, with minimal anatomic changes in air space morphology. The weight of the posterior mediastinal lymph node draining the lung and the gastrointestinal tract doubled, inducible nitric oxide synthase (NOSII)-positive cells increased, and Foxp3-positive T-regulatory lymphocytes decreased in the lymph node after IL-1 alpha exposure. In the blood, neutrophil counts and plasma haptoglobin increased after IL-1 alpha exposure. Compared with a single exposure, exposure to intra-amniotic IL-1 alpha 7 days and again 1 day before delivery had a variable effect (increases in some inflammatory markers, but not pulmonary cytokines). IL-1 alpha is a potent mediator of the fetal inflammatory response syndrome.