Division of Clinical Nutrition, Department of Food and Nutrition, Japan Women's University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo, 112-8681, Japan.
Inflammation. 2018 Oct;41(5):1842-1851. doi: 10.1007/s10753-018-0827-2.
Maternal health and nutritional status influence offspring health and the diseases that may develop in them. The effects of maternal inflammation on offspring from the perspective of the inflammatory response and immune changes are not fully understood. We hypothesized that maternal inflammation modulates immune and metabolic functions, affecting the pathophysiology of inflammatory diseases in offspring. This study investigated whether maternal inflammation affects the onset of collagen-induced arthritis (CIA), a murine model of human rheumatoid arthritis. Female DBA/1J mice received a single intraperitoneal injection of lipopolysaccharide (LPS) 5 days before conception. Male offspring of LPS-treated dams were placed in the maternal LPS group (MLG). To induce CIA, type II collagen (CII) was emulsified with Freund's complete adjuvant and injected twice into each mouse, at 13 and 16 weeks. The offspring were sacrificed at 26 weeks to analyze immunological and metabolic parameters. The degree of joint swelling at an early stage of CIA was lower in the MLG than in the control group. From histological analysis, the severity of joint destruction (severity of arthritis score) and CII-specific IgG titer were significantly lower in the MLG. However, at 26 weeks, serum interleukin (IL)-6 levels, an index of CIA disease activity, were significantly higher in the MLG. Moreover, serum leptin levels were lower in the MLG, and a negative correlation between leptin and serum IL-6 was observed. In conclusion, maternal inflammation does not merely suppress inflammation; it may delay CIA in offspring. The analysis of inflammatory cytokines and leptin concentrations at 26 weeks suggests that the pathophysiology of arthritis was worsening. This study also suggests that maternal inflammation modulates postnatal inflammatory response patterns in offspring.
母体健康和营养状况影响后代的健康以及他们可能患上的疾病。母体炎症对后代炎症反应和免疫变化的影响尚不完全清楚。我们假设母体炎症会调节免疫和代谢功能，影响后代炎症性疾病的病理生理学。本研究探讨了母体炎症是否会影响胶原诱导关节炎（CIA）的发病，CIA 是人类类风湿关节炎的一种小鼠模型。雌性 DBA/1J 小鼠在受孕前 5 天接受单次腹腔注射脂多糖（LPS）。LPS 处理的母鼠的雄性后代被置于母体 LPS 组（MLG）。为了诱导 CIA，将 II 型胶原（CII）与福氏完全佐剂混合，并两次注射到每只小鼠中，分别在 13 周和 16 周。在 26 周时处死后代，以分析免疫和代谢参数。CIA 早期，MLG 组的关节肿胀程度低于对照组。从组织学分析来看，关节破坏的严重程度（关节炎评分严重程度）和 CII 特异性 IgG 滴度在 MLG 中显著降低。然而，在 26 周时，MLG 中的血清白细胞介素（IL）-6 水平，CIA 疾病活动的指标，显著升高。此外，MLG 中的血清瘦素水平较低，并且观察到瘦素与血清 IL-6 之间存在负相关。总之，母体炎症不仅不会抑制炎症，反而可能会延迟后代的 CIA。对 26 周时炎症细胞因子和瘦素浓度的分析表明关节炎的病理生理学正在恶化。本研究还表明，母体炎症会调节后代出生后的炎症反应模式。
