PDF(Pubmed)
Abstract：
The prevalence of prenatal alcohol exposure (PAE) is increasing, with evidence suggesting that PAE is linked to an increased risk of infections. PAE is hypothesized to affect the innate immune system, which identifies pathogens through pattern recognition receptors, of which toll-like receptors (TLRs) are key components. We hypothesized that light-to-moderate PAE would impair immune responses, as measured by a heightened response in cytokine levels following TLR stimulation. Umbilical cord samples (10 controls and 8 PAE) from a subset of the Ethanol, Neurodevelopment, Infant and Child Health Study-2 cohort were included. Peripheral blood mononuclear cells (PMBCs) were stimulated with one agonist (TLR2, TLR3, TLR4, or TLR9). TLR2 agonist stimulation significantly increased pro-inflammatory interleukin-1-beta in the PAE group after 24 h. Pro- and anti-inflammatory cytokines were increased following stimulation with the TLR2 agonists. Stimulation with TLR3 or TLR9 agonists displayed minimal impact overall, but there were significant increases in the percent change of the control compared to PAE after 24 h. The results of this pilot investigation support further work into the impact on TLR2 and TLR4 response following PAE to delineate if alterations in levels of pro- and anti-inflammatory cytokines have clinical significance that could be used in patient management and/or attention to follow-up.
摘要：
产前酒精暴露（PAE）的患病率正在增加，有证据表明PAE与感染风险增加有关。PAE被认为会影响先天免疫系统，通过模式识别受体识别病原体，其中Toll样受体(TLRs)是关键成分。我们假设轻度至中度PAE会损害免疫反应，如通过TLR刺激后细胞因子水平的增强反应所测量的。来自乙醇子集的脐带样本（10个对照和8个PAE），神经发育,纳入婴儿和儿童健康研究-2队列。用一种激动剂(TLR2、TLR3、TLR4或TLR9)刺激外周血单核细胞(PMBCs)。TLR2激动剂刺激在24小时后显著增加PAE组中的促炎性白介素-1-β。在用TLR2激动剂刺激后,促炎性和抗炎细胞因子增加。用TLR3或TLR9激动剂刺激显示总体影响最小,但24小时后与PAE相比，对照组的变化百分比显着增加。这项初步研究的结果支持进一步研究PAE后对TLR2和TLR4反应的影响，以确定促炎和抗炎细胞因子水平的变化是否具有可用于患者管理和/或关注随访的临床意义。
