Strunk Tobias, van Haren Simon D, Hibbert Julie, Pettengill Matthew, Ozonoff Al, Jans Jop, Schüller Simone S, Burgner David, Levy Ofer, Currie Andrew J
Centre for Neonatal Research and Education, University of Western Australia, Perth, WA, Australia.
Neonatal Directorate, King Edward Memorial Hospital, Perth, WA, Australia.
Pediatr Res. 2020 Nov;88(5):717-725. doi: 10.1038/s41390-019-0586-2. Epub 2019 Oct 2.
Preterm 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.
Cord 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.
cAMP 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.
The 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.
早产儿感染风险高，且具有独特的病原体识别反应。推测的机制包括可提高细胞内环磷酸腺苷（cAMP）水平的可溶性介质。本研究的目的是评估出生后第一个月婴儿血中cAMP浓度与Toll样受体（TLR）介导的细胞因子产生之间的关系。
从一组极早产儿（胎龄<30周）和足月儿中获取脐带血及系列外周血样本（出生后1 - 28天）。采用酶联免疫吸附测定（ELISA）和多重微珠检测法测量全血中cAMP、FSL - 1以及体外脂多糖（LPS）刺激后的细胞因子浓度。
脐带血中cAMP浓度高于外周血，女性早产儿脐带血中cAMP浓度更高，且即使校正白细胞计数后，暴露于绒毛膜羊膜炎的婴儿在出生第1天和第7天时cAMP浓度仍较低。早产儿出生后第一个月内，体外TLR2和TLR4介导的肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-12p70和白细胞介素-10的产生增加，且与校正白细胞后的cAMP水平呈正相关，并因暴露于绒毛膜羊膜炎而降低。
血中cAMP浓度的个体发育以及与绒毛膜羊膜炎和TLR介导的细胞因子产生的关联表明，这种第二信使有助于在生命早期塑造独特的新生儿病原体反应。
