Kramer Boris W, Ikegami Machiko, Moss Timothy J M, Nitsos Ilias, Newnham John P, Jobe Alan H
University Children's Hospital, Josef-Schneider-Str. 2, 97080 Wuerzburg, Germany.
Am J Respir Crit Care Med. 2005 Jan 1;171(1):73-7. doi: 10.1164/rccm.200406-745OC. Epub 2004 Oct 1.
The preterm fetus is immune naive and has immature innate immune function. Although the preterm fetus is frequently exposed to chorioamnionitis, the effects of exposure of the fetal lung to inflammation on innate immune responses are unknown. Using the fetal sheep model of chorioamnionitis, cord blood monocytes were isolated from preterm lambs 1 to 14 days after intra-amniotic endotoxin injection, cultured for approximately 16 hours, and challenged with endotoxin in vitro. Compared with monocytes from adult sheep, the preterm monocytes produced less H(2)O(2) and interleukin-6, and toll-like receptor 4 expression was decreased. Three days after intra-amniotic endotoxin exposure, preterm monocyte responses to in vitro endotoxin challenge demonstrated decreased H(2)O(2) and interleukin-6 production and decreased CD14 and major histocompatibility complex class II expression. Preterm monocyte responses 7 to 14 days after endotoxin tended to exceed those of adults and preterm control animals indicating augmented function. In contrast, a second intra-amniotic endotoxin injection 7 days after the initial endotoxin exposure suppressed monocyte function at 14 days. The fetal monocytes demonstrated patterns of responses consistent with endotoxin tolerance (immune paralysis) as well as maturation of function. Modulation of fetal innate immune responses by exposure to inflammation may alter subsequent immune adaptation after birth.
早产胎儿免疫功能未成熟且处于免疫初始状态。尽管早产胎儿经常暴露于绒毛膜羊膜炎，但胎儿肺部暴露于炎症对先天性免疫反应的影响尚不清楚。利用绒毛膜羊膜炎的胎羊模型，在羊膜腔内注射内毒素后1至14天，从早产羔羊中分离脐血单核细胞，培养约16小时，然后在体外向内毒素发起挑战。与成年绵羊的单核细胞相比，早产单核细胞产生的过氧化氢和白细胞介素-6较少，且Toll样受体4表达降低。羊膜腔内暴露于内毒素三天后，早产单核细胞对体外内毒素挑战的反应表现为过氧化氢和白细胞介素-6产生减少，以及CD14和主要组织相容性复合体II类表达降低。内毒素暴露7至14天后，早产单核细胞的反应往往超过成年动物和早产对照动物，表明其功能增强。相比之下，在初次内毒素暴露7天后再次进行羊膜腔内内毒素注射，会在14天时抑制单核细胞功能。胎儿单核细胞表现出与内毒素耐受（免疫麻痹）以及功能成熟相一致的反应模式。暴露于炎症对胎儿先天性免疫反应的调节可能会改变出生后随后的免疫适应。
