Paediatrics, Trinity College, the University of Dublin, Dublin, Ireland.
Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, Dublin, Ireland.
BMC Immunol. 2018 Nov 3;19(1):31. doi: 10.1186/s12865-018-0270-z.
Down syndrome (DS) is the most common syndromic immunodeficiency with an increased risk of infection, mortality from sepsis, and autoinflammation. Innate immune function is altered in DS and therefore we examined responses in CD11b and Toll like receptor 4 (TLR-4), which are important immune cell surface markers upregulated in response to Lipopolysaccharide (LPS) endotoxin, and the immunomodulator melatonin. Neutrophil and monocyte responses to LPS and melatonin in children with Down syndrome (DS) who were clinically stable were compared to age-matched controls. Whole blood was incubated with LPS and melatonin and the relative expression of CD11b and TLR-4 evaluated by flow cytometry.
Children with DS had an increased response to LPS in neutrophils and intermediate monocytes, while also having elevated TLR-4 expression on non-classical monocytes compared to controls at baseline. Melatonin reduced CD11b expression on neutrophils, total monocytes, both classical and intermediate sub-types, in children with DS and controls.
Melatonin could represent a useful clinical adjunct in the treatment of sepsis as an immunomodulator. Children with DS had increased LPS responses which may contribute to the more adverse outcomes seen in sepsis.
唐氏综合征（DS）是最常见的综合征免疫缺陷，感染风险增加，败血症死亡率增加，自身炎症。DS 患者的固有免疫功能发生改变，因此我们研究了 CD11b 和 Toll 样受体 4（TLR-4）的反应，这是对脂多糖（LPS）内毒素和免疫调节剂褪黑素上调的重要免疫细胞表面标志物。与年龄匹配的对照组相比，比较了临床稳定的唐氏综合征（DS）儿童对 LPS 和褪黑素的中性粒细胞和单核细胞反应。用 LPS 和褪黑素孵育全血，并通过流式细胞术评估 CD11b 和 TLR-4 的相对表达。
DS 儿童中性粒细胞和中间单核细胞对 LPS 的反应增加，而与对照组相比，非经典单核细胞的 TLR-4 表达也升高。褪黑素降低了 DS 儿童和对照组中性粒细胞、总单核细胞、经典和中间亚型的 CD11b 表达。
褪黑素作为免疫调节剂，可作为治疗败血症的有用临床辅助手段。DS 儿童对 LPS 的反应增加，这可能导致败血症的不良后果更严重。
