Modulation of pro- and anti-inflammatory cytokine production in very preterm infants
Modulation of pro- and anti-inflammatory cytokine production in very preterm infants
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DOI：
10.1016/s1043-4666(02)00498-2
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发表时间：
2003-02-21
期刊：
影响因子：
3.8
通讯作者：
Bartmann, P
中科院分区：
文献类型：
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作者：
Dembinski, J;Behrendt, D;Bartmann, P
背景资料：在早产儿中，尽管抗生素治疗和诊断取得了进展，但感染相关并发症的结局仍不一致。关于早产儿免疫反应的信息有限。免疫调节策略需要对介质及其动力学进行详细分析。目的：在体外脐带血培养（CBC）内毒素模型中确定早产儿和足月儿中IL-1 β、TNF α、IL-6、IL-8、IL-10、γ INF和G-CSF的动力学。设计和方法：25名婴儿出生后立即从胎盘的胎儿侧获得脐带血，并在培养基中孵育（RPMI 1640）在存在或不存在500 pg/ml脂多糖（LPS）的情况下培养48 h。通过连续免疫测定法（IMMULITE（R）. DPC Biermann，德国）; IL-10（Milenia Biotec，Bad瑙海姆.德国）。在0、4、8、12、24和48小时通过ELISA测定上清液中的γ INF（Diaclone，贝桑松，法国）和G-CSF（R & D Systems，威斯巴登，德国）。婴儿被分为三个胎龄组（小于或等于32周、33-36周、大于或等于37周）。首先通过Kruskal-Wallis检验分析组间差异的显著性，并通过Manti-Whitney-U检验比较配对。用线性回归分析法检验胎龄、白细胞计数、红细胞压积和产前激素暴露频率对妊娠结局的影响。为了纠正可能的影响变量，白细胞计数，细胞因子水平进行了调整，根据个人的白细胞numbers.Results：LPS刺激的最大水平的IL-6，IL-1 β，TNF α和G-CSF在全血细胞计数显着低于非常早产儿相比，更先进的胎龄组。在调整10（5）个白细胞的细胞因子水平后，检测到胎龄对IL-6和G-CSF产生的显著影响（p < 0.05）。在多次产前类固醇暴露后，观察到细胞因子水平降低的非显著趋势。白细胞介素-10（IL-10）：TNF-α的比例增加非常早产儿相比，先进的胎龄，虽然增加不显着。结论：促炎细胞因子活性CBC与胎龄相关，而IL-10没有。尽管CBC中IL-1 β、TNF α、IL-6、G-CSF的体外合成部分取决于白细胞数量，但IL-6和G-CSF的合成似乎与不成熟有关。产前多次类固醇暴露和早产儿IL-10：TNF α比值升高的非显著影响新生儿，在小样本量中观察到，值得进一步研究。(C)2003爱思唯尔科技有限公司版权所有。
Background: In premature infants, outcome of infection-associated complications is heterogeneous despite advances in antibiotic treatment and diagnosis. Information on the immune response in preterm infants is limited. Immune modulatory strategies require detailed analysis of mediators and their kinetics.Objective: To determine the kinetics of IL-1beta, TNFalpha, IL-6, IL-8, IL-10, gammaINF and G-CSF in preterm and term infants in an ex vivo cord blood culture (CBC) endotoxin model.Design and methods: Cord blood of 25 infants was obtained immediately after birth from the fetal side of the placenta and incubated in culture medium (RPMI 1640) in the presence or absence of 500 pg/ml lipopolysaccharide (LPS) for 48 h. TNFalpha, IL-1beta, IL-6 and IL-8 were measured by sequential immunometric assay (IMMULITE(R). DPC Biermann, Germany); IL-10 (Milenia Biotec, Bad Nauheim. Germany). gammaINF (Diaclone, Besancon, France) and G-CSF (R & D Systems, Wiesbaden, Germany) were determined by ELISA in supernatants at 0, 4, 8, 12, 24 and 48 h. Infants were stratified into three gestational age groups (less than or equal to32 weeks, 33-36 weeks, greater than or equal to37 weeks.). Variations between the groups were first analyzed for significance by Kruskal-Wallis test and pairs were compared by Manti-Whitney-U test. Effects of gestational age, leucocyte Count, hematocrit and frequency of antenatal steroid exposure were tested by linear regression analysis. To correct a possible impact of variable, WBC count, cytokine levels were adjusted according to individual leucocyte numbers.Results: LPS-stimulated maximum levels of IL-6, IL-1beta, TNFalpha and G-CSF in CBC were significantly lower in very preterm infants compared to more advanced gestational age groups. After adjusting the cytokine levels for 10(5) leucocytes, a significant effect of gestational age on IL-6 and G-CSF production (p < 0.05) was detected. A non-significant trend towards reduced cytokine levels was observed following multiple antenatal steroid exposures. IL-10: TNFalpha ratio increased in very preterm neonates when compared with the advanced gestational age, although the increase was not significant.Conclusions: Pro-inflammatory cytokine activity in CBC correlates with gestational age, whereas IL-10 does not. Although ex vivo synthesis of IL-1beta, TNFalpha, IL-6, G-CSF in CBC depends in part on leucocyte numbers, IL-6 and G-CSF synthesis appeared to be related to immaturity. Non-significant effects of multiple antenatal steroid exposure and increased IL-10: TNFalpha ratio in preterm. neonates, observed in a small sample size, warrant further investigation. (C) 2003 Elsevier Science Ltd. All rights reserved.