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Increased systemic inflammation in children with Down syndrome
Cytokine ( IF 3.8 ) Pub Date : 2020-03-01 , DOI: 10.1016/j.cyto.2019.154938
Dean Huggard 1 , Lynne Kelly 2 , Emer Ryan 2 , Fiona McGrane 3 , Niamh Lagan 3 , Edna Roche 3 , Joanne Balfe 3 , T Ronan Leahy 4 , Orla Franklin 5 , Derek G Doherty 2 , Eleanor J Molloy 6
Affiliation  

Children with Down syndrome (DS) develop more infections, have an increased mortality from sepsis and an increased incidence of chronic inflammatory conditions. Cytokine dysregulation may underpin these clinical sequelae and raised pro-inflammatory biomarkers are a feature in adults with DS. The importance of the anti-inflammatory mediators IL-1ra and IL-10, as well as cytokines Epo and VEGF, which could impact on the pathogenesis and outcomes in congenital heart disease (CHD) which is more prevalent in DS, are less well known. We examined a comprehensive array of pro-(IL-2, IL-6, IL-8, IL-18, IL-1β, TNF-α, IFN-γ), and anti-inflammatory (IL-10 and IL-1ra) mediators, cytokines involved in inflammation in response to hypoxia (EPO), propagating angiogenesis (VEGF), and myelopoiesis (GM-CSF), by enzyme linked immunosorbent assay (ELISA), as well as discussing the potential impact of significant CHD and Lipopolysaccharide endotoxin on these mediators. 114 children with DS and 60 age and sex matched controls were recruited. Children with Down syndrome exhibit significantly greater levels of pro and anti-inflammatory cytokines; IL-2, IL-6, IL-10, IL-1ra, as well as increased Epo, VEGF and GM-CSF at baseline. CHD does not seem to have an impact on circulating cytokines beyond the acute surgical phase. Both cohorts had similar responses to LPS stimulation. These differences may contribute to varied clinical outcomes, acutely like in sepsis, and over time in autoimmunity.

中文翻译:

唐氏综合症患儿全身炎症增加

患有唐氏综合症 (DS) 的儿童感染更多,败血症死亡率增加,慢性炎症的发病率增加。细胞因子失调可能是这些临床后遗症的基础,升高的促炎生物标志物是 DS 成人的一个特征。抗炎介质 IL-1ra 和 IL-10 以及细胞因子 Epo 和 VEGF 的重要性可能影响先天性心脏病 (CHD)(在 DS 中更为普遍)的发病机制和结果,但鲜为人知. 我们检查了一系列的 pro-(IL-2、IL-6、IL-8、IL-18、IL-1β、TNF-α、IFN-γ)和抗炎(IL-10 和 IL-1ra ) 通过酶联免疫吸附试验 (ELISA) 检测参与响应缺氧 (EPO)、增殖血管生成 (VEGF) 和骨髓细胞生成 (GM-CSF) 的炎症的介质、细胞因子,以及讨论显着 CHD 和脂多糖内毒素对这些介质的潜在影响。招募了 114 名 DS 儿童和 60 名年龄和性别匹配的对照组。患有唐氏综合症的儿童表现出更高水平的促炎和抗炎细胞因子;IL-2、IL-6、IL-10、IL-1ra 以及基线 Epo、VEGF 和 GM-CSF 增加。在急性手术阶段之后,CHD 似乎对循环细胞因子没有影响。两个队列对 LPS 刺激的反应相似。这些差异可能导致不同的临床结果,如脓毒症,以及随着时间的推移在自身免疫中。患有唐氏综合症的儿童表现出更高水平的促炎和抗炎细胞因子;IL-2、IL-6、IL-10、IL-1ra 以及基线 Epo、VEGF 和 GM-CSF 增加。在急性手术阶段之后,CHD 似乎对循环细胞因子没有影响。两个队列对 LPS 刺激的反应相似。这些差异可能导致不同的临床结果,如脓毒症,以及随着时间的推移在自身免疫中。患有唐氏综合症的儿童表现出更高水平的促炎和抗炎细胞因子;IL-2、IL-6、IL-10、IL-1ra 以及基线 Epo、VEGF 和 GM-CSF 增加。在急性手术阶段之后,CHD 似乎对循环细胞因子没有影响。两个队列对 LPS 刺激的反应相似。这些差异可能导致不同的临床结果,如脓毒症,以及随着时间的推移在自身免疫中。
更新日期:2020-03-01
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