
支气管肺发育不良患儿血清白细胞介素33的水平变化及临床意义
Changes of serum interleukin-33 in preterm infants with bronchopulmonary dysplasia
目的 探讨白细胞介素33(IL-33)在早产儿支气管肺发育不良(BPD)发生、发展中的作用及意义。方法 本研究采用前瞻性队列研究,选取胎龄≤32周和/或出生体重≤1 500 g的早产儿128例,根据病情分为非BPD组50例,轻度BPD组32例,中度BPD组30例,重度BPD组16例,收集所有早产儿母亲产前因素(母亲产前使用激素、母亲绒毛膜羊膜炎)、患儿产时因素(性别、胎龄、出生体重、分娩方式、出生窒息)、生后治疗情况(肺表面活性物质、有创通气时间、无创通气时间、肠外营养时间、总住院时间);对各组早产儿分别于生后第1天、第14天、第28天采用酶联免疫吸附试验(ELISA)法检测血清IL-33水平,比较不同组别生后不同时间血清IL-33水平差异;对中重度BPD患儿确诊后采用传统激素治疗(DART方案),检测治疗前后两组间血清IL-33水平变化。结果 BPD早产儿在母亲感染绒毛膜羊膜炎、胎龄、出生体重、出生窒息、有创通气时间、无创通气时间、肠外营养时间、总住院时间等方面,与非BPD早产儿比较,差异均有统计学意义(P < 0.05),且上述指标在不同病情严重程度BPD早产儿组间比较差异有统计学意义(P < 0.05)。早产儿生后第1天、第14天、第28天,BPD组患儿血清IL-33水平高于非BPD组,且BPD病情程度越重,IL-33水平越高;随着生后时间的推移,BPD患儿血清IL-33水平有升高趋势(P < 0.05)。中重度BPD早产儿采用DART方案治疗后血清IL-33水平较治疗前均降低(P < 0.05)。结论 血清IL-33与BPD发生及病情严重程度密切相关,DART方案抗炎治疗可降低BPD患儿血清IL-33水平。
Objective To study the role of interleukin-33 (IL-33) in the development and progression of bronchopulmonary dysplasia (BPD) in preterm infants. Methods A prospective cohort study was performed on 128 preterm infants with a gestational age of ≤ 32 weeks and/or a birth weight of ≤ 1 500 g. They were classified to a non-BPD group with 50 infants, a mild BPD group with 32 infants, a moderate BPD group with 30 infants, and a severe BPD group with 16 infants. Related data were collected, including antepartum factors of mothers (antepartum hormone and chorioamnionitis), intrapartum factors of preterm infants (sex, gestational age, birth weight, mode of birth, and birth asphyxia), treatment after birth (pulmonary surfactant, duration of invasive ventilation, duration of noninvasive ventilation, duration of parenteral nutrition, and length of hospital stay). The high-risk factors for BPD were analyzed. ELISA was used to measure the serum level of IL-33 in preterm infants on days 1, 14, and 28 after birth. The serum level of IL-33 was compared between groups at different time points after birth. The preterm infants with moderate or severe BPD were treated with conventional corticosteroid therapy (DART regimen), and the serum level of IL-33 was measured before and after treatment. Results There were significant differences between the preterm infants with BPD and those without BPD in the incidence of maternal chorioamnionitis, gestational age, birth weight, the incidence of birth asphyxia, duration of invasive ventilation, duration of noninvasive ventilation, duration of parenteral nutrition, and total length of hospital stay (P < 0.05). There were significant differences in the above indices among the preterm infants with different severities of BPD (P < 0.05). On days 1, 14, and 28 after birth, the infants with BPD had a significantly higher serum level of IL-33 than those without BPD, and the serum level of IL-33 tended to increase with the severity of BPD and over the time after birth (P < 0.05). The preterm infants with moderate or severe BPD had a significant reduction in the serum level of IL-33 after the treatment with DART regimen (P < 0.05). Conclusions Serum IL-33 is closely associated with the development and severity of BPD. Anti-inflammatory therapy with DART regimen can decrease the serum level of IL-33.
Bronchopulmonary dysplasia / Interleukin-33 / Preterm infant
[1] 陈超, 袁琳. 早产儿支气管肺发育不良的病因及危险因素[J]. 中国实用儿科杂志, 2014, 29(1):5-7.
[2] Cakir U, Tayman C, Yucel C. A novel diagnostic marker for the severity of bronchopulmonary dysplasia in very low birth weight infants:interleukin-33[J]. Pediatr Allergy Immunol Pulmonol, 2019, 32(1):12-17.
[3] Lal CV, Ambalavanan N. Cellular and humoral biomarkers of bronchopulmonary dysplasia[J]. Early Hum Dev, 2017, 105:35-39.
[4] Tang X. Interleukin-33(IL-33) increases hyperoxia-induced bronchopulmonary dysplasia in newborn mice by regulation of inflammatory mediators[J]. Med Sci Monit, 2018, 24:6717-6728.
[5] de Kleer IM, Kool M, de Bruijn MJ, et al. Perinatal activation of the interleukin-33 pathway promotes type 2 immunity in the developing lung[J]. Immunity, 2016, 45(6):1285-1298.
[6] 邵肖梅, 叶鸿瑁, 丘小汕. 实用新生儿学[M]. 第5版. 北京:人民卫生出版社, 2019:596-601.
[7] 早产儿支气管肺发育不良调查协作组. 早产儿支气管肺发育不良发生率及高危因素的多中心回顾调查分析[J]. 中华儿科杂志, 2011, 49(9):655-662.
[8] Davidson LM, Berkelhamer SK. Bronchopulmonary dysplasia:chronic lung disease of infancy and long-term pulmonary outcomes[J]. J Clin Med, 2017, 6(1):4.
[9] Kersbergen KJ, de Vries LS, van Kooij BJ, et al. Hydrocortisone treatment for bronchopulmonary dysplasia and brain volumes in preterm infants[J]. J Pediatr, 2013, 163(3):666-671.e1.
[10] Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease[J]. Nat Rev Immunol, 2016, 16(11):676-689.
[11] Nabe T, Wakamori H, Yano C, et al. Production of interleukin (IL)-33 in the lungs during multiple antigen challenge-induced airway inflammation in mice, and its modulation by a glucocorticoid[J]. Eur J Pharmacol, 2015, 757:34-41.
[12] Christianson CA, Goplen NP, Zafar I, et al. Persistence of asthma requires multiple feedback circuits involving type 2 innate lymphoid cells and IL-33[J]. J Allergy Clin Immunol, 2015, 136(1):59-68.e14.
[13] Ding W, Zou GL, Zhang W, et al. Interleukin-33:its emerging role in allergic diseases[J]. Molecules, 2018, 23(7):1665.
[14] Griesenauer B, Paczesny S. The ST2/IL-33 axis in immune cells during inflammatory diseases[J]. Front Immunol, 2017, 8:475.
[15] Chen WY, Tsai TH, Yang JL, et al. Therapeutic strategies for targeting IL-33/ST2 signalling for the treatment of inflammatory diseases[J]. Cell Physiol Biochem, 2018, 49(1):349-358.