Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris AP-HP, 75019, Paris, France.
Univ. Paris Diderot, Sorbonne Paris Cité, Paris, France.
Pediatr Res. 2019 Jul;86(1):63-70. doi: 10.1038/s41390-019-0383-y. Epub 2019 Mar 31.
Altered production of cytokines is believed to contribute to early childhood susceptibility to infection. The aim of this study was to get further insight into the developmental patterns of cytokine responses from birth to adulthood.
The expression levels of 13 cytokines were compared in the supernatants of phytohemaggluttinin (PHA)-stimulated whole blood from healthy neonates (cord blood, n = 8), infants ( < 1-year-old, n = 20), and school-aged children (3-15 y; n = 20). Five adults were used as reference.
While Th1, Th2, and Th17 cytokine levels increased progressively from birth to childhood (Mann-Whitney, p < 0.003), high IL-10 secretion at birth dropped to low adult levels in infants (p < 0.004) such that a negative correlation between IL-10 and Th1, Th2, and Th17 cytokine levels at birth (Spearman's correlation, r < -0.70, p < 0.01) converted to a positive correlation in infants (r > 0.60, p < 0.001). Finally, high IL-2, IL-7, and Granulocyte-Colony Stimulating factor (G-CSF) cytokine levels at birth decreased steadily over the first year of life (Mann-Whitney, p ≤ 0.001).
The most noticeable result of the study is the rapid shift from enhanced IL-10 secretion capacity at birth toward balanced IL-10/Th1/Th2/Th17 cytokine levels early in life. This change appears an essential precondition to fight pathogens and at the same time to avoid overwhelming inflammatory reactions.
细胞因子产生的改变被认为是导致儿童早期易感染的原因之一。本研究旨在进一步深入了解从出生到成年期间细胞因子反应的发育模式。
比较了健康新生儿(脐血,n=8)、婴儿(<1 岁,n=20)和学龄儿童(3-15 岁;n=20)的植物血凝素(PHA)刺激全血上清液中 13 种细胞因子的表达水平。使用 5 名成年人作为参考。
Th1、Th2 和 Th17 细胞因子水平从出生到儿童期逐渐增加(Mann-Whitney,p<0.003),出生时高 IL-10 分泌在婴儿期下降至成人低水平(p<0.004),导致出生时 IL-10 与 Th1、Th2 和 Th17 细胞因子水平之间的负相关(Spearman 相关,r<−0.70,p<0.01)在婴儿期转换为正相关(r>0.60,p<0.001)。最后,出生时高 IL-2、IL-7 和粒细胞集落刺激因子(G-CSF)细胞因子水平在生命的第一年中稳步下降(Mann-Whitney,p≤0.001)。
本研究最显著的结果是从出生时增强的 IL-10 分泌能力迅速转变为生命早期平衡的 IL-10/Th1/Th2/Th17 细胞因子水平。这种变化似乎是对抗病原体同时避免过度炎症反应的必要前提。