Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-α production in vitro and in vivo
Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-α production in vitro and in vivo
复制标题
DOI：
10.1203/01.pdr.0000228319.10481.ea
复制
发表时间：
2006-08-01
影响因子：
3.6
通讯作者：
Levy, Ofer
中科院分区：
文献类型：
--
作者：
Angelone, Donatella F.;Wessels, Michael R.;Levy, Ofer
人类新生儿易受微生物感染，这些感染与新生儿免疫系统不完全确定的方面有关。为了表征新生儿先天免疫，我们研究了在体外对toll样受体（TLR）激活的微生物刺激产生的两种早期反应细胞因子：促炎细胞因子肿瘤坏死因子(TNF)- α和IL-6，一种具有抗炎和th2极化特性的多功能细胞因子。新生儿脐带血对多种TLR激动剂的反应，包括聚dI:dC （TLR3）、脂多糖（LPS） （TLR4）、鞭毛蛋白（TLR5）和CpG DNA (TLR9)，其特征是IL-6/ tnf - α比高于成人外周血。强力脂多糖诱导的IL-6产生是由于新生儿细胞（单核细胞-）和不道德（血清-）因素。值得注意的是，在出生后第一周收集的新生儿血清显示出比脐带血更高的IL-6/TNF-a比率，这与IL-6诱导的急性期反应物CRP和lps结合蛋白在出生后最初几天的升高有关。刺激诱导的高比例IL-6/TNF-a的产生可能深刻地调节人类新生儿的先天和适应性免疫反应。
Human newborns are susceptible to microbial infection related to incompletely defined aspects of the neonatal immune system. To characterize neonatal innate immunity, we studied production of two early response cytokines in response to Toll-like receptor (TLR) -activating microbial stimuli in vitro: the proinflammatory cytokine tumor necrosis factor (TNF)-alpha and IL-6, a multifunctional cytokine with antinflammatory and Th2-polarizing properties. Neonatal cord blood responses to multiple TLR agonists, including poly dI:dC (TLR3), lipopolysaccharide (LPS) (TLR4), flagellin (TLR5), and CpG DNA (TLR9), are characterized by a higher IL-6/TNF-alpha ratio than in adult peripheral blood. Robust LPS-induced IL-6 production is due to both neonatal cellular (monocyte-) and Immoral (serum-) factors. Remarkably, serum collected from newborns during the first week of life demonstrates higher IL-6/TNF-a ratios than does cord blood, associated with elevations of the IL-6-inducible acute phase reactants CRP and LPS-binding protein in the first days of life. A high ratio of stimulus-induced IL-6/TNF-a production is likely to profoundly modulate both innate and adaptive immune responses in the human newborn.