Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro.
Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro.
复制标题
人类早产儿血液中的环 AMP 与体外 TLR 介导的急性期和抗炎细胞因子的产生增加有关。
DOI：
10.1038/s41390-019-0586-2
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发表时间：
2020
影响因子：
3.6
通讯作者：
Currie,AndrewJ
中科院分区：
文献类型：
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作者：
Strunk,Tobias;vanHaren,SimonD;Hibbert,Julie;Pettengill,Matthew;Ozonoff,Al;Jans,Jop;Schüller,SimoneS;Burgner,David;Levy,Ofer;Currie,AndrewJ
研究背景早产儿是感染的高危人群，具有明显的病原体识别反应。建议的机制包括可溶性介质，提高细胞水平的cAMP。本研究的目的是评估血液cAMP浓度和TLR介导的细胞因子的生产在婴儿在第一个月的life.MethodsCord和系列外周血样本（天的生活1-28）之间的关系，从一个队列的非常早产儿（<30周的胎龄）和足月人类婴儿。全血中cAMP和FSL-1和LPS在体外刺激的细胞因子浓度测定ELISA和多重珠assay.ResultscAMP浓度高于在外周血中，更高的女性早产儿的脐带血中，和较低的第1和第7天的婴儿暴露于绒毛膜炎，即使调整后的白细胞计数。TLR 2和TLR 4介导的TNF-α、IL-1β、IL-6、IL-12 p70，和IL-10的体外生产增加了超过第一个月的早产儿的生活，并与白细胞调整cAMP水平呈正相关，并减少了接触绒毛膜炎。介导的细胞因子的产生表明，这种第二信使有助于在生命早期形成不同的新生儿病原体反应。
BackgroundPreterm infants are at high risk of infection and have distinct pathogen recognition responses. Suggested mechanisms include soluble mediators that enhance cellular levels of cAMP. The aim of this study was to assess the relationship between blood cAMP concentrations and TLR-mediated cytokine production in infants during the first month of life.MethodsCord and serial peripheral blood samples (days of life 1–28) were obtained from a cohort of very preterm (<30 weeks’ gestational age) and term human infants. Whole-blood concentrations of cAMP and FSL-1 and LPS in vitro stimulated cytokine concentrations were measured by ELISA and multiplex bead assay.ResultscAMP concentrations were higher in cord than in peripheral blood, higher in cord blood of female preterm infants, and lower at Days 1 and 7 in infants exposed to chorioamnionitis, even after adjusting for leukocyte counts. TLR2 and TLR4-mediated TNF-α, IL-1β, IL-6, IL-12p70, and IL-10 production in vitro increased over the first month of life in preterm infants and were positively correlated with leukocyte-adjusted cAMP levels and reduced by exposure to chorioamnionitis.ConclusionsThe ontogeny of blood cAMP concentrations and associations with chorioamnionitis and TLR-mediated production of cytokines suggest that this secondary messenger helps shape distinct neonatal pathogen responses in early life.