Marchant Elizabeth A, Kan Bernard, Sharma Ashish A, van Zanten Alice, Kollmann Tobias R, Brant Rollin, Lavoie Pascal M
Child & Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Pediatr Res. 2015 Nov;78(5):492-7. doi: 10.1038/pr.2015.132. Epub 2015 Jul 17.
Antimicrobial responses have been shown to be profoundly attenuated in very preterm neonates when examined on cord blood. However, we lack data on these responses at the time these neonates are most vulnerable to infections.
Multiple cytokine responses to two prototypic Toll-like receptor (TLR) agonists: lipopolysaccharide (LPS) (TLR4) and R848 (TLR7/8) were prospectively measured in preterm neonates born ≤30 wk of gestation (n = 50) during the first 28 d of age using whole blood and single-cell multiparameter flow cytometry assays. Results were compared to term neonates (n = 30) and adult controls (n = 25).
In preterm neonates, LPS and R848 responses remained attenuated in both cord blood and in the first 28 d of age. These responses showed significant maturation over time after adjusting for gestational age and were confirmed in monocytes and dendritic cells on a per-cell basis. We detected no major contribution of chorioamnionitis, maternal antenatal corticosteroids or magnesium sulfate treatment, labor, or mode of delivery to the maturation of cytokine responses.
Innate immune antimicrobial defenses are profoundly attenuated developmentally in very preterm neonates during the neonatal period, suggesting that exogenous factors drive the sustained systemic inflammation that has been linked to increased morbidities in these infants.
对脐血进行检测时发现，极早产儿的抗菌反应显著减弱。然而，我们缺乏这些新生儿在最易感染时的此类反应数据。
前瞻性地测量了出生时胎龄≤30周（n = 50）的早产儿在出生后28天内对两种典型Toll样受体（TLR）激动剂：脂多糖（LPS）（TLR4）和R848（TLR7/8）的多种细胞因子反应，采用全血和单细胞多参数流式细胞术检测。将结果与足月儿（n = 30）和成人对照组（n = 25）进行比较。
在早产儿中，LPS和R848反应在脐血和出生后的前28天内均减弱。在调整胎龄后，这些反应随时间推移显示出显著成熟，并且在单核细胞和树突状细胞中以单个细胞为基础得到证实。我们未发现绒毛膜羊膜炎、母亲产前使用糖皮质激素或硫酸镁治疗、分娩或分娩方式对细胞因子反应成熟有重大影响。
在新生儿期，极早产儿的先天性免疫抗菌防御在发育上显著减弱，这表明外源性因素导致了与这些婴儿发病率增加相关的持续性全身炎症。
