维生素C对新生儿脐血细胞胞质内细胞因子产生的免疫调节作用。

Immunomodulatory effect of vitamin C on intracytoplasmic cytokine production in neonatal cord blood cells.

作者信息

Hartel Christoph, Puzik Alexander, Gopel Wolfgang, Temming Petra, Bucsky Peter, Schultz Christian

机构信息

Department of Pediatrics, University of Lubeck Medical School, Lubeck, Germany.

出版信息

Neonatology. 2007;91(1):54-60. doi: 10.1159/000096972. Epub 2006 Nov 10.

DOI:10.1159/000096972

PMID:17344653

Abstract

BACKGROUND

Vitamin C (ascorbic acid) is an essential water-soluble antioxidant in cells and plasma. Besides metabolic functions, vitamin C is also known to contribute to immune homeostasis. Recently, it has been demonstrated that vitamin C has an inhibitory effect on the expression of pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha) in adult whole blood cells in vitro. It has been postulated that vitamin C might be an interesting compound for modulation of an over-exuberant immune response, e.g., in patient cohorts susceptible for the development of systemic inflammatory response syndrome such as neonates. It was the aim of this study to investigate the modulatory effects of vitamin C on the production of inflammatory mediators in neonatal cord blood cells.

METHODS

The intracytoplasmic production of pro-inflammatory cytokines in neonatal cord blood cells stimulated with lipopolysaccharide or phorbol 12-myristate 13-acetate/ionomycin was assessed by flow-cytometry.

RESULTS

In contrast to our previous observations from adult whole blood cells, 20 mM vitamin C mildly stimulated the percentage of neonatal monocytes producing IL-6 after lipopolysaccharide stimulation (e.g., 11.3% increase compared to control, p = 0.005). In the presence of 20 mM vitamin C, even a stronger stimulatory effect was noted for the percentage of IL-8 (e.g., 46.7% increase, p < 0.001) and TNF-alpha producing neonatal monocytes (e.g., 69.2% increase, p = 0.004; n = 20). In accordance with adult data, the percentage of neonatal lymphocytes producing IL-2 after phorbol 12-myristate 13-acetate/ionomycin stimulation was dose-dependently reduced (e.g., 41.3% inhibition, p = 0.001, 20 mM vitamin C), while the percentage of TNF-alpha producing lymphocytes was mildly stimulated (e.g., 20.8% increase, p = 0.003, 20 mM vitamin C).

CONCLUSIONS

Interestingly, vitamin C was demonstrated to enhance pro-inflammatory responses in CD14(+) cord blood cells while only intracellular IL-2 production in CD3(+) cells was diminished. These data suggest that vitamin C differentially influences intracytoplasmic cytokine production in adults and neonates, and further studies are needed to elucidate the underlying mechanisms of this selective immunomodulation.

摘要

背景

维生素C（抗坏血酸）是细胞和血浆中一种必需的水溶性抗氧化剂。除代谢功能外，维生素C还对免疫稳态有作用。最近，体外实验表明维生素C对成人全血细胞中促炎细胞因子如白细胞介素（IL）-6和肿瘤坏死因子α（TNF-α）的表达有抑制作用。据推测，维生素C可能是一种用于调节过度活跃免疫反应的有趣化合物，例如在易发生全身炎症反应综合征的患者群体如新生儿中。本研究旨在探讨维生素C对新生儿脐血细胞中炎症介质产生的调节作用。

方法

通过流式细胞术评估用脂多糖或佛波醇12-肉豆蔻酸酯13-乙酸酯/离子霉素刺激后新生儿脐血细胞中促炎细胞因子的胞内产生情况。

结果

与我们之前对成人全血细胞的观察结果相反，20 mM维生素C在脂多糖刺激后轻度刺激了产生IL-6的新生儿单核细胞百分比（例如，与对照组相比增加了11.3%，p = 0.005）。在存在20 mM维生素C的情况下，观察到对产生IL-8的新生儿单核细胞百分比（例如，增加了46.7%，p < 0.001）和产生TNF-α的新生儿单核细胞百分比（例如，增加了69.2%，p = 0.004；n = 20）有更强的刺激作用。与成人数据一致，在佛波醇12-肉豆蔻酸酯13-乙酸酯/离子霉素刺激后，产生IL-2的新生儿淋巴细胞百分比呈剂量依赖性降低（例如，20 mM维生素C时抑制41.3%，p = 0.001），而产生TNF-α的淋巴细胞百分比受到轻度刺激（例如，20 mM维生素C时增加20.8%，p = 0.003）。