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健康儿童的细胞因子谱分析显示细胞因子浓度与年龄有关。

Cytokine profiling in healthy children shows association of age with cytokine concentrations.

机构信息

Infectious Diseases and Vaccinology Unit, University of Basel Children's Hospital, 4056, Basel, Switzerland.

Paediatric Pharmacology and Pharmacometrics, University of Basel Children's Hospital, 4056, Basel, Switzerland.

出版信息

Sci Rep. 2017 Dec 19;7(1):17842. doi: 10.1038/s41598-017-17865-2.

Abstract

Cytokine-based diagnostic assays are increasingly used in research and clinical practice. Assays developed for adults such as the interferon-gamma release assay for tuberculosis show inferior performance in children. Limited evidence suggests that release of cytokines is influenced by age but normal ranges of cytokines in children are lacking. Whole blood of healthy children (0-12 years) undergoing elective/diagnostic procedures was stimulated with SEB, PHA, Candida albicans for 24 hours or left unstimulated. Concentrations of eight cytokines were measured by multiplex bead-based immunoassays and associations with age and other factors quantified by regression analysis. 271 children (median age 5.2 years) were included. In unstimulated samples IL-1ra, IP-10 and TNF-α concentrations decreased by up to -60% with age. Following antigen stimulation, an age-associated increase (ranging from +90% to +500%) was observed for all cytokines except IL-1ra (significant for IL-4, IFN-γ and TNF-α). Inter-individual variability in cytokine concentrations was large with a coefficient of variation ranging from 42% to 1412%. Despite inter-individual variation age was identified as a strong influencing factor of cytokine concentrations. Age-specific normal values need to be considered for cytokine-based diagnostic purposes. These results are relevant for development of novel cytokine-based diagnostic assays and for optimal dosing of therapeutic agents targeting cytokines.

摘要

基于细胞因子的诊断检测在研究和临床实践中得到了越来越多的应用。为成年人开发的检测方法,如干扰素-γ释放检测(IGRA)在儿童中表现不佳。有限的证据表明,细胞因子的释放受年龄影响,但缺乏儿童细胞因子的正常范围。接受选择性/诊断性操作的健康儿童(0-12 岁)的全血用 SEB、PHA、白色念珠菌刺激 24 小时或不刺激。通过多重珠基免疫分析测量八种细胞因子的浓度,并通过回归分析量化与年龄和其他因素的关联。共纳入 271 名儿童(中位数年龄为 5.2 岁)。在未刺激的样本中,IL-1ra、IP-10 和 TNF-α 的浓度随年龄下降高达 -60%。在抗原刺激后,除 IL-1ra 外(IL-4、IFN-γ 和 TNF-α 有统计学意义),所有细胞因子的浓度均呈年龄相关增加(范围从+90%到+500%)。细胞因子浓度的个体间变异性很大,变异系数范围为 42%至 1412%。尽管存在个体间差异,但年龄被确定为细胞因子浓度的一个重要影响因素。为了基于细胞因子的诊断目的,需要考虑年龄特异性的正常值。这些结果对于开发新的基于细胞因子的诊断检测方法以及针对细胞因子的治疗药物的最佳剂量具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee0e/5736560/4d7c52328c4a/41598_2017_17865_Fig1_HTML.jpg

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