Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation

Abstract

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 interleukins 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 125I IL-6 i.v. to pregnant dams at gestation day 11-13 (mid-gestation) or 17-19 (late gestation). We found 125I-IL-6 in the exposed fetuses as well as in amniotic fluids. Fetal 125I-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 125I-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.