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牙龈沟液中 T 细胞相关细胞因子的阵列分析:鉴定与牙周病状态相关的改变的特征谱。

Array analysis for T-cell associated cytokines in gingival crevicular fluid: Identifying altered profiles associated with periodontal disease status.

机构信息

School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.

School of Dentistry, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff, UK.

出版信息

J Dent. 2019 Jun;85:39-46. doi: 10.1016/j.jdent.2019.04.009. Epub 2019 Apr 24.

Abstract

OBJECTIVE

Cytokine networks regulate innate and adaptive immune responses, which in turn are recognised to direct the progression or arrest of periodontal disease. This study aimed to compare the profile of seven cytokines, implicated in regulating T-cell networks, in gingival crevicular fluid (GCF) samples with differing classification of periodontal status.

METHODS

GCF samples were collected from patients with strong clinical evidence for chronic periodontitis, aggressive periodontitis, gingivitis or no gingival inflammation. Cytokines IL-6, IFN-ɣ, IL-4, IL-2, IL-17 A, IL10 and TNFα were measured in each sample using a commercial cytometric bead array assay. Descriptive statistics were used to indicate central tendency, data scatter and analysis of variance for each cytokine concentrations between respective patient groups. Heat maps with dendrograms were produced to visualise hierarchical clustering and trends within the data.

RESULTS

Median concentrations for all cytokines analysed were highest for gingivitis samples and lowest for aggressive periodontitis samples. The median concentration of IL-6 in gingivitis samples was observed to be 10.5 fold higher (˜17,300 pg/μl) than IL-6 in aggressive periodontitis samples (˜1600 pg/μl). Median concentrations of IL-10, IL-17 A and TNFα were also 2-2.2 fold higher in gingivitis samples compared to aggressive periodontitis.

CONCLUSIONS

Descriptive statistical analysis noted raised concentrations of IL-6, IL-17 A and TNFα associated with gingivitis; pro-inflammatory cytokines usually associated with periodontal tissue destruction, including bone. Our results would suggest that these cytokines can additionally provide protective roles in preventing progression to advanced forms of periodontal disease. Potential for how these cytokines contribute to providing this role is discussed.

CLINICAL SIGNIFICANCE

Defining the roles for the many cytokines involved in the pathogenesis of periodontal disease is far from complete. Consequently the results of this study serve to evidence proposals that cytokines can exhibit both pro- and anti-inflammatory effects, which is dependent on the signalling environment within which they exist and the antagonizing or modifying actions of other cytokines. Whilst future research is necessary to explore mechanistic action, our study contributes new knowledge suggesting that IL-6 and IL-17 A can provide roles in stabilising the lesion to limit disease progression, which does not preclude alternative roles in promoting periodontal bone loss in advanced forms of disease progression, which is also documented in the literature.

摘要

目的

细胞因子网络调节先天和适应性免疫反应,而这些反应又被认为可以指导牙周病的进展或停止。本研究旨在比较牙龈沟液(GCF)样本中七种细胞因子的特征,这些细胞因子与牙周状况的不同分类有关。

方法

从患有慢性牙周炎、侵袭性牙周炎、牙龈炎或无牙龈炎症的患者中采集 GCF 样本。使用商业细胞因子 bead 阵列测定法测量每个样本中的细胞因子 IL-6、IFN-ɣ、IL-4、IL-2、IL-17A、IL10 和 TNFα。使用描述性统计数据表示中心趋势、数据分散和每个细胞因子浓度在相应患者组之间的方差分析。制作热图和聚类图以直观地显示数据中的层次聚类和趋势。

结果

所有分析细胞因子的中位数浓度在牙龈炎样本中最高,在侵袭性牙周炎样本中最低。在牙龈炎样本中观察到 IL-6 的中位数浓度比侵袭性牙周炎样本高 10.5 倍(约 17,300pg/μl),而在侵袭性牙周炎样本中 IL-6 的中位数浓度约为 1600pg/μl。在牙龈炎样本中,IL-10、IL-17A 和 TNFα 的中位数浓度也比侵袭性牙周炎样本高 2-2.2 倍。

结论

描述性统计分析注意到与牙龈炎相关的 IL-6、IL-17A 和 TNFα 浓度升高;通常与牙周组织破坏(包括骨)相关的促炎细胞因子。我们的结果表明,这些细胞因子在防止牙周病进展为更严重形式方面可能具有保护作用。讨论了这些细胞因子如何发挥这种作用的潜力。

临床意义

定义参与牙周病发病机制的许多细胞因子的作用还远远没有完成。因此,这项研究的结果证明了细胞因子可以表现出促炎和抗炎作用,这取决于它们存在的信号环境以及其他细胞因子的拮抗或修饰作用。尽管未来的研究有必要探索其作用机制,但我们的研究提供了新的知识,表明 IL-6 和 IL-17A 可以在稳定病变方面发挥作用,从而限制疾病的进展,这并不排除它们在促进疾病进展的晚期形式中的牙周骨丢失方面的替代作用,这在文献中也有记载。

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