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梅尼埃病患者血清中NLRP6炎性小体与炎性细胞因子IL-1β和IL-18水平的相关性

Correlation between NLRP6 inflammasome and the levels of inflammatory cytokines IL-1b and IL-18 in serum of patients with Meniere's disease.

作者信息

Li Mengxiao, Zhou Ying, Liu Zhibiao, Jin Xin

机构信息

The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Department of Otolaryngology-Head and Neck Surgery, Huaian, China.

出版信息

J Med Biochem. 2025 Jul 4;44(4):740-747. doi: 10.5937/jomb0-55001.

Abstract

BACKGROUND

Meniere's disease (MD) is a prevalent condition in otolaryngology, with its annual incidence rate increasing. Consequently, understanding the underlying mechanisms of MD is of significant importance. The aim is to investigate the relationship between serum levels of interleukin-1b (IL-1b) and interleukin-18 (IL-18), as well as the activation status of NLRP6 inflammasomes, in patients with Meniere's disease and to evaluate their correlation with the severity of the disease, to improve the treatment strategy of Meniere's disease.

METHODS

From March 2021 to December 2023, 75 MD patients were selected from the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University for research, and a control group consisting of 75 age-matched healthy individuals was established. Each participant contributed a 5 mL peripheral venous blood sample, which was archived at -80 °C for subsequent analyses. The expression levels of NLRP6 messenger RNA in the blood samples were quantified using real-time fluorescence quantitative PCR methodology. Concentrations of interleukin-1b (IL-1b) and interleukin-18 (IL-18) were measured via enzyme-linked immunosorbent assay (ELISA). Through a comparative examination of NLRP6, IL-1b, and IL-18 levels between MD patients and the healthy controls, the study delved into the potential association between NLRP6 expression and the circulating levels of these two cytokines. In addition, special attention is paid to the differences between unilateral and bilateral MD patients in the above three indexes to evaluate their effectiveness as potential biomarkers for predicting the severity of hearing loss in MD patients.

RESULTS

In individuals suffering from MD, a notable elevation was observed in the peripheral blood expression levels of NLRP6, IL-1b, and IL-18 (p<0.001). A correlation assessment disclosed a positive association between the blood NLRP6 content and both IL-1b and IL-18 concentrations among these patients. Notably, no substantial disparity emerged in the expression profiles of these three biomarkers when comparing unilateral versus bilateral MD cases (p>0.05). Furthermore, patients at advanced stages (III+IV) exhibited significantly heightened levels of NLRP6, IL-1b, and IL-18 compared to their counterparts in earlier stages (I+II) (p<0.001). Receiver operating characteristic (ROC) curve analyses demonstrated that the area under the curve (AUC) for NLRP6, IL-1b, and IL-18 stood at 0.8731, 0.8089, and 0.7838, respectively, suggesting their potential as proficient diagnostic markers capable of differentiating MD patients from healthy controls.

CONCLUSIONS

NLRP6, IL-1b, and IL-18 are highly expressed in the peripheral blood of MD patients. NLRP6, IL-1b, and IL-18 can serve as early diagnostic indicators for MD.

摘要

背景

梅尼埃病(MD)是耳鼻喉科的一种常见病症,其年发病率呈上升趋势。因此,了解MD的潜在发病机制具有重要意义。目的是研究梅尼埃病患者血清白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)水平以及NLRP6炎性小体的激活状态之间的关系,并评估它们与疾病严重程度的相关性,以改进梅尼埃病的治疗策略。

方法

2021年3月至2023年12月,从南京医科大学附属淮安第一人民医院选取75例MD患者进行研究,并建立了由75名年龄匹配的健康个体组成的对照组。每位参与者提供5 mL外周静脉血样本,保存在-80°C以备后续分析。采用实时荧光定量PCR方法定量检测血样中NLRP6信使核糖核酸的表达水平。通过酶联免疫吸附测定(ELISA)检测白细胞介素-1β(IL-1β)和白细胞介素-18(IL-18)的浓度。通过比较MD患者和健康对照之间的NLRP6、IL-1β和IL-18水平,该研究深入探讨了NLRP6表达与这两种细胞因子循环水平之间的潜在关联。此外,特别关注单侧和双侧MD患者在上述三个指标上的差异,以评估它们作为预测MD患者听力损失严重程度的潜在生物标志物的有效性。

结果

在MD患者中,观察到外周血中NLRP6、IL-1β和IL-18的表达水平显著升高(p<0.001)。相关性评估显示,这些患者血液中NLRP6含量与IL-1β和IL-18浓度之间呈正相关。值得注意的是,比较单侧与双侧MD病例时,这三种生物标志物的表达谱没有显著差异(p>0.05)。此外,晚期(III+IV)患者的NLRP6、IL-1β和IL-18水平明显高于早期(I+II)患者(p<0.001)。受试者工作特征(ROC)曲线分析表明,NLRP6、IL-1β和IL-18的曲线下面积(AUC)分别为0.8731、0.8089和0.7838,表明它们有可能作为区分MD患者和健康对照的有效诊断标志物。

结论

NLRP6、IL-1β和IL-18在MD患者外周血中高表达。NLRP6、IL-1β和IL-18可作为MD的早期诊断指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f5e/12363349/a73241561b4d/jomb-44-4-2504740L_g001.jpg

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