Müller K, Zak M, Nielsen S, Pedersen F K, de Nully P, Bendtzen K
Department of Pediatrics GGK, National University Hospital, Copenhagen, Denmark.
Pediatr Allergy Immunol. 1996 Aug;7(3):117-24. doi: 10.1111/j.1399-3038.1996.tb00118.x.
Age related differences in immunological reactions include variations in the in vitro functions of blood mononuclear cells (MNC). In an attempt to understand the mechanism behind these differences we examined age related differences in the phenotype profiles of MNC in parallel with the in vitro production of interleukin IL-6, tumour necrosis factor alpha (TNF alpha) and interferon gamma (IFNg) in neonates, children and adults. In cultures without added polyclonal activators IL-6 and TNF alpha levels in children were 3-6 times higher than those of umbilical cords and adults. However, using optimal in vitro stimulation (E. coli lipopolysaccharide (LPS), phytohaemmagglutinin or pokeweed mitogen (PWM)) no significant differences in the levels of these cytokines were observed. The levels of IFNg in PWM driven cultures followed a different pattern with comparable levels in children and adults, and unmeasurable levels in cord blood MNC. Flow cytometry analysis of the phenotypic distribution of MNC revealed age related differences in the expression of CD3, CD4, CD8, CD14, CD19, CD45RA, CD45R0, CD2, LFA-1, ICAM-1 and LFA-3. Correlation studies did not indicate that the observed differences in cytokine production could be ascribed to differences in the frequency of monocytes, T cells or B cells. The TNF alpha levels in suboptimally stimulated cultures correlated negatively with the expression of LFA-3 and positively with CD45RA, while IFNg correlated positively with CD2, LFA-1, CD45R0 and CD8. In conclusion, the study provides evidence of age related differences in the production of TNF alpha, IL-6 and IFNg among neonates, children and adults. These differences may to some extent be caused by differences in the expression of cell surface molecules involved in cellular interactions and signalling.
免疫反应中的年龄相关差异包括血液单核细胞（MNC）体外功能的变化。为了理解这些差异背后的机制，我们检测了新生儿、儿童和成人MNC表型谱的年龄相关差异，并同时检测了白细胞介素IL-6、肿瘤坏死因子α（TNFα）和干扰素γ（IFNγ）的体外产生情况。在未添加多克隆激活剂的培养物中，儿童体内IL-6和TNFα水平比脐带血和成人高3至6倍。然而，使用最佳体外刺激（大肠杆菌脂多糖（LPS）、植物血凝素或商陆丝裂原（PWM））时，未观察到这些细胞因子水平有显著差异。PWM驱动培养物中的IFNγ水平呈现不同模式，儿童和成人中的水平相当，而脐带血MNC中的水平无法检测到。MNC表型分布的流式细胞术分析揭示了CD3、CD4、CD8、CD14、CD19、CD45RA、CD45R0、CD2、淋巴细胞功能相关抗原-1（LFA-1）、细胞间黏附分子-1（ICAM-1）和淋巴细胞功能相关抗原-3（LFA-3）表达的年龄相关差异。相关性研究并未表明观察到的细胞因子产生差异可归因于单核细胞、T细胞或B细胞频率的差异。次优刺激培养物中的TNFα水平与LFA-3的表达呈负相关，与CD45RA呈正相关，而IFNγ与CD2、LFA-1、CD45R0和CD8呈正相关。总之，该研究提供了证据表明新生儿、儿童和成人在TNFα、IL-6和IFNγ产生方面存在年龄相关差异。这些差异可能在一定程度上是由参与细胞相互作用和信号传导的细胞表面分子表达差异引起的。
