Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan,
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Neonatology. 2023;120(3):353-362. doi: 10.1159/000529679. Epub 2023 Mar 30.
Interleukin (IL)-33 and its receptor ST2L play key roles in the IL-33/ST2 signaling pathway. Soluble ST2 (sST2) inhibits the proper function of IL-33. sST2 levels are increased in patients with several neurological diseases, but in infants with hypoxic-ischemic encephalopathy (HIE), IL-33 and sST2 levels have not been studied. This study aimed to investigate whether serum levels of IL-33 and sST2 are useful as biomarkers of HIE severity and prognostic factors for infants with HIE.
Twenty-three infants with HIE and 16 controls (gestational age ≥36 weeks and ≥1,800 g birth weight) were enrolled in this study. Serum levels of IL-33 and sST2 were measured at <6 h, 1-2, 3, and 7 days of age. Hydrogen-1 magnetic resonance spectroscopy was performed, and ratios of peak integrals of lactate/N-acetylaspartate (Lac/NAA) were calculated as objective indicators of brain damage.
In the moderate and severe HIE, serum sST2 concentrations were increased and there was a good correlation between serum sST2 and HIE severity on days 1-2, whereas no variation was observed in serum IL-33. Serum sST2 levels were positively correlated with Lac/NAA ratios (Kendall's rank correlation coefficient = 0.527, p = 0.024), and both sST2 and Lac/NAA ratios were significantly higher in HIE infants with neurological impairment (p = 0.020 and <0.001, respectively).
sST2 may be a useful predictor of severity and later neurological outcomes in infants with HIE. Further investigation is required to elucidate the relationship between the IL-33/ST2 axis and HIE.
白细胞介素 (IL)-33 和其受体 ST2L 在 IL-33/ST2 信号通路中发挥关键作用。可溶性 ST2（sST2）抑制 IL-33 的正常功能。几种神经疾病患者的 sST2 水平升高，但在患有缺氧缺血性脑病 (HIE) 的婴儿中，尚未研究 IL-33 和 sST2 水平。本研究旨在探讨血清 IL-33 和 sST2 水平是否可作为 HIE 严重程度的生物标志物以及 HIE 婴儿的预后因素。
本研究纳入了 23 名 HIE 婴儿和 16 名对照婴儿（胎龄≥36 周，出生体重≥1800 g）。在出生后<6 h、1-2、3 和 7 天测量血清 IL-33 和 sST2 水平。进行氢-1 磁共振波谱分析，并计算乳酸/N-乙酰天冬氨酸 (Lac/NAA) 峰积分比作为脑损伤的客观指标。
在中重度 HIE 中，血清 sST2 浓度升高，且在第 1-2 天，血清 sST2 与 HIE 严重程度之间存在良好的相关性，而血清 IL-33 无变化。血清 sST2 水平与 Lac/NAA 比值呈正相关（Kendall 等级相关系数=0.527，p=0.024），且 HIE 伴有神经功能障碍的婴儿的 sST2 和 Lac/NAA 比值均显著升高（p=0.020 和<0.001）。
sST2 可能是预测 HIE 婴儿严重程度和后续神经结局的有用指标。需要进一步研究阐明 IL-33/ST2 轴与 HIE 之间的关系。
