Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation
Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation
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DOI：
10.1203/01.pdr.0000230026.74139.18
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发表时间：
2006-08-01
影响因子：
3.6
通讯作者：
Holmang, Agneta
中科院分区：
文献类型：
--
作者：
Dahlgren, Jovanna;Samuelsson, Anne-Maj;Holmang, Agneta
妊娠期间的母体感染可能使胎儿暴露于感染剂和高水平的炎症反应介质，如IL-6(IL-6)。胎儿和母亲IL-6水平的升高与不良的新生儿结局有关，但也可能给胎儿带来压力，并在成年后导致心血管和神经内分泌功能障碍。目前尚不清楚白细胞介素2是否穿过胎盘屏障，尽管这方面的研究很少。因此，这项研究的目的是调查体内给药的妊娠大鼠的IL-6是否会转移到胎儿。我们静脉注射了I-125、IL-6。在妊娠第11-13天(中期)或17-19天(妊娠晚期)向怀孕的水母发放。我们在暴露的胎儿和羊水中发现了I-125-IL-6。妊娠中期注射的动物胎儿I-125-IL-6水平明显高于妊娠晚期(p<；0.01)。这种差异反映在妊娠中期母儿对I-125-IL-6的单向清除量增加了15倍(p<；0.01)。结论：妊娠中期大鼠胎盘屏障对IL-6的通透性明显高于妊娠晚期。母体来源的IL-6可直接导致胎儿损伤，但也可刺激胎儿应激激素的释放，导致神经内分泌结构和激素轴的刺激或侮辱，从而可能导致成年后的疾病。
Maternal systemic infection during pregnancy may expose the fetus to infectious agents and high levels of mediators of the resulting inflammatory response, such as IL-6 (IL-6). Increased fetal and maternal levels of IL-6 have been associated with adverse neonatal outcome but might also stress the fetus and contribute to cardiovascular and neuroendocrine dysfunction in adulthood. It is unclear whether interleukines cross the placental barrier, although this matter has been little studied. The aim of this study was therefore to investigate if IL-6 administered to pregnant rats in vivo is transferred to the fetus. We injected I-125 IL-6 i.v. to pregnant dams at gestation day 11-13 (mid-gestation) or 17-19 (late gestation). We found I-125-IL-6 in the exposed fetuses as well as in amniotic fluids. Fetal I-125-IL-6 levels were markedly higher in animals injected in mid-gestation compared with late pregnancy (p < 0.01). This difference was mirrored in a 15-fold higher unidirectional materno-fetal clearance for I-125-IL-6 in mid-gestation (p < 0.01). We conclude that the permeability of the rat placental barrier to IL-6 is much higher in mid-gestation than in late pregnancy. Maternally derived IL-6 may directly induce fetal injury but also stimulate the release of fetal stress hormones resulting in stimuli or insults in neuroendocrine structures and hormonal axes which might lead to disease at adult age.