Cytokine Profiles in Asthma Families Depend on Age and Phenotype

Cytokine Profiles in Asthma Families Depend on Age and Phenotype
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DOI:
10.1371/journal.pone.0014299
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发表时间:
2010-12-13
期刊:
影响因子:
3.7
通讯作者:
Wjst, Matthias
Wjst, Matthias
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Pukelsheim, Katrin;Stoeger, Tobias;Wjst, Matthias

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背景资料:循环细胞因子模式可能与哮喘的诊断、某些表型的鉴别和疾病恶化的预后因素有关。方法学/主要发现:在这项研究中,我们调查了来自218个受哮喘影响的家庭的944个个体的血清样本,通过多重微球系统以高灵敏度检测11种哮喘相关介质:嗜酸性粒细胞趋化因子(CCL 11)、粒细胞巨噬细胞刺激因子(GM-CSF)、干扰素γ(IFN γ)、白细胞介素-4(IL-4)、IL-5、IL-8、IL-10、IL-12(p40)、IL-13、IL-17和肿瘤坏死因子α(TNF α)。当分析哮喘作为单一疾病实体时,哮喘和健康个体之间的单一细胞因子水平基本相似。父母和儿童哮喘之间的调节差异反映在分析的11种介质中的6种(嗜酸性粒细胞趋化因子、IL-4、IL-5、IL-10、IL-12、TNF α)。IL-12(p40)和IL-5是儿童外源性哮喘的最佳预测因子,每log pg/ml增加的比值比分别为2.85和1.96(IL-12(p40):1.2-6.8,p = 0.019,IL-5:1.2-2.5,p = 0.025)。儿童哮喘频繁发作与血清IL-5水平升高相关(p = 0.013)。细胞因子模式似乎在健康和患病的成人和儿童中个体平衡,各种细胞因子相互关联(IL-17和IFN γ(r(s)= 0.67),IL-4和IL-5(r(s)= 0.55),IFN γ和GM-CSF(r(s)= 0.54))。我们的数据主要支持一种年龄依赖性的全身免疫调节,但也支持一种哮喘表型依赖性的全身免疫调节。
Background: Circulating cytokine patterns may be relevant for the diagnosis of asthma, for the discrimination of certain phenotypes, and prognostic factors for exacerbation of disease.Methodology/Principal Findings: In this study we investigated serum samples from 944 individuals of 218 asthma-affected families by a multiplex, microsphere based system detecting at high sensitivity eleven asthma associated mediators: eotaxin (CCL11), granulocyte macrophage stimulating factor (GM-CSF), interferon gamma (IFN gamma), interleukin-4 (IL-4), IL-5, IL-8, IL-10, IL-12 (p40), IL-13, IL-17 and tumor necrosis factor alpha (TNF alpha). Single cytokine levels were largely similar between asthmatic and healthy individuals when analysing asthma as single disease entity. Regulatory differences between parental and pediatric asthma were reflected by six of the eleven mediators analyzed (eotaxin, IL-4, IL-5, IL-10, IL-12, TNF alpha). IL-12 (p40) and IL-5 were the best predictor for extrinsic asthma in children with an increased odds ratio of 2.85 and 1.96 per log pg/ml increase (IL-12 (p40): 1.2-6.8, p = 0.019, and IL-5: 1.2-2.5, p = 0.025). Frequent asthma attacks in children are associated with elevated IL-5 serum levels (p = 0.013). Cytokine patterns seem to be individually balanced in both, healthy and diseased adults and children, with various cytokines correlating among each other (IL-17 and IFN gamma (r(s) = 0.67), IL-4 and IL-5 (r(s) = 0.55), IFN gamma and GM-CSF (r(s) = 0.54)).Conclusion/Significance: Our data support mainly an age-but also an asthma phenotype-dependent systemic immune regulation.