Systemic inflammation in pregnant obese women is associated with 1.5- to 2-fold increase in serum Interleukin-6 (IL-6) and newborns with lower kidney/body weight ratio but the role of IL-6 in increased susceptibility to chronic kidney (CKD) in adult progeny is not known. Since IL-6 crosses the placental barrier, we administered recombinant IL-6 (10 pg/g) to pregnant mice starting at mid-gestation yielded newborns with lower body (p < 0.001) and kidney (p < 0.001) weights. Histomorphometry indicated decreased nephrogenic zone width (p = 0.039) with increased numbers of mature glomeruli (p = 0.002) and pre-tubular aggregates (p = 0.041). Accelerated maturation in IL-6 newborns was suggested by early expression of podocyte-specific protein podocin in glomeruli, increased 5-methyl-cytosine (LC–MS analysis for CpG DNA methylation) and altered expression of certain genes of cell-cycle and apoptosis (RT-qPCR array-analysis). Western blotting showed upregulated pJAK2/pSTAT3. Thus, treating dams with IL-6 as a surrogate provides newborns to study effects of maternal systemic inflammation on future susceptibility to CKD in adulthood.

肥胖孕妇的全身炎症与血清白细胞介素 6 (IL-6) 和肾脏/体重比较低的新生儿增加 1.5 至 2 倍有关，但 IL-6 在增加慢性肾病 (CKD) 易感性中的作用) 在成年后代中尚不清楚。由于 IL-6 穿过胎盘屏障，我们从妊娠中期开始向怀孕小鼠施用重组 IL-6 (10 pg/g)，产生下半身 (p < 0.001) 和肾脏 (p < 0.001) 重量的新生儿。组织形态测定表明，随着成熟肾小球 (p = 0.002) 和肾小管前聚集体 (p = 0.041) 数量的增加，肾源性区宽度减小 (p = 0.039)。足细胞特异性蛋白 podocin 在肾小球中的早期表达表明 IL-6 新生儿加速成熟，增加 5-甲基胞嘧啶（CpG DNA 甲基化的 LC-MS 分析）并改变某些细胞周期和细胞凋亡基因的表达（RT-qPCR 阵列分析）。蛋白质印迹显示 pJAK2/pSTAT3 上调。因此，用 IL-6 作为替代物治疗大坝为新生儿提供了研究母体全身炎症对未来成年期 CKD 易感性的影响。