40 Gestational choline supplementation prevents inflammatory responses of lipopolysaccharide-induced preeclampsia in pregnant rats

Abstract

Introduction Pre-eclampsia (PE) exerts more intense systemic inflammatory response than normal pregnancy. We have demonstrated that the cholinergic anti-inflammatory pathway may contribute to the relief of Pre-eclampsia through α 7 nicotinic acetylcholine receptor ( α 7 nAChR). Furthermore, choline, an essential nutrient that is meanwhile a selective α 7 nAChR agonist, has been proved to prevent LPS-induced preeclampsia symptoms in rats. Objectives The objective of the study was to examine the effects of choline, an essential nutrient that is meanwhile a selective α 7 nAChR agonist, on the prevention of symptoms and inflammatory responses of preeclampsia in rats. Methods Preeclampsia model was induced by lipopolysaccharide (1.0 μ g/kg) via tail vein injection on gestational day (GD) 14. Pregnant SD rats were placed on a supplemented (5.0 g/kg diet) or normal (1.1 g/kg diet) choline diet throughout gestation. All the rats were divided into 4 groups (P = normal pregnant +1.1 g/kg choline diet; P-CHOLINE = normal pregnant +5.0 g/kg choline diet; PE = LPS +1.1 g/kg choline diet; PE-CHOLINE = LPS +5.0 g/kg choline diet). Maternal blood and placentas were collected on GD20 and assayed for pro-inflammatory cytokines (TNF- α , IL-1 β , IL-6, IL-2, IL-17, IFN- γ , GM-CSF) and anti-inflammatory cytokines (IL-4, IL-10). Results LPS treatment significantly elevates maternal blood levels of TNF- α , IL-1 β , IL-6, IL-17, IFN- γ , GM-CSF and reduced the levels of IL-4. The blood levels of IL-2 and IL-10 show no significant differences between the P and PE group. Of interest, choline supplementation during pregnancy significantly inhibited LPS-induced release of TNF-a, IL-1 β , IL-6, IL-17, IFN- γ , except for GM-CSF , and increased the level of IL-4. Correspondingly, in placenta, the levels of TNF- α , IL-1 β , IL-6, IL-17, GM-CSF and IL-2 were significantly increased after LPS administration, while the level of IL-4 was significantly decreased. The placenta levels of IFN- γ and IL-10 show no significant differences between the P and PE group. Similarly, choline supplementation during pregnancy significantly attenuated LPS-induced TNF- α , IL-1 β , IL-6 and IL-17 concentrations, except for IL-2, meanwhile, increased the level of IL-4. Conclusions Choline supplementation during pregnancy prevents the LPS-induced symptoms and inflammatory responses of preeclampsia in rats. These observations have important implications for prevention of inflammatory responses in preeclampsia.