Huang Chao, Wang Qin, Pan Xueying, Li Wei, Liu Wei, Jiang Wenqi, Huang Li, Peng Anquan, Zhang Zhiwen
Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
Department of Anesthesiology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Front Neurol. 2022 Feb 23;13:781031. doi: 10.3389/fneur.2022.781031. eCollection 2022.
Immune mediated inflammatory changes affecting the endolymphatic sac (ES) may underlie the pathology of Meniere's disease (MD). The aim of the present study was to explore the differentially expressed cytokines in ES luminal fluid (ELF) of patients with MD, and the correlation between the expression of cytokines in the ELF with that in the serum was determined by quantitatively analyzing the cytokines in human ELF and serum.
Human ELF, serum and ES tissues were collected from patients with unilateral MD and patients with acoustic neuroma (AN) during surgery. The Simoa Cytokine 6-Plex Panel kit was used to analyze the levels of cytokines in the ELF and blood samples of the patients. Immunohistochemistry and immunofluorescence were subsequently used to validate the relative expression levels of the cytokines in MD.
Significant differences were identified in the expression levels of interferon-γ (IFN-γ) ( < 0.001), interleukin (IL)-6 ( = 0.008) and tumor necrosis factor-α (TNF-α) ( = 0.036) in the luminal fluid of the ES comparing between the MD and AN groups. By contrast, the levels of IFN-γ, IL-10, IL-12p70, IL-17A, IL-6 and TNF-α in the serum of the MD group were not significantly different from those of either the AN group or healthy control subjects. In addition, no significant correlations in the expression levels of cytokines compared between the ELF and serum were found for the patients in either the MD or the AN group. Finally, the detection of positive expression of TNF-α, IL-6 and IFN-γ in the epithelial cells of the majority of ES specimens from patients with MD confirmed the up-regulated expression of these cytokines in the ES of patients with MD.
The identification of up-regulated expression levels of TNF-α, IL-6 and IFN-γ in the ELF in the present study has provided direct evidence for an increased immunologic activity in the microenvironment of the ES in patients with unilateral MD, may suggest the local inflammatory response underlies the mechanism of this disease.
影响内淋巴囊（ES）的免疫介导性炎症变化可能是梅尼埃病（MD）发病机制的基础。本研究旨在探讨MD患者ES腔液（ELF）中细胞因子的差异表达，并通过定量分析人ELF和血清中的细胞因子，确定ELF中细胞因子表达与血清中细胞因子表达之间的相关性。
在手术过程中收集单侧MD患者和听神经瘤（AN）患者的人ELF、血清和ES组织。使用Simoa细胞因子6联检试剂盒分析患者ELF和血样中的细胞因子水平。随后采用免疫组织化学和免疫荧光法验证MD中细胞因子的相对表达水平。
MD组和AN组ES腔液中干扰素-γ（IFN-γ）（<0.001）、白细胞介素（IL）-6（=0.008）和肿瘤坏死因子-α（TNF-α）（=0.036）的表达水平存在显著差异。相比之下，MD组血清中IFN-γ、IL-10、IL-12p70、IL-17A、IL-6和TNF-α的水平与AN组或健康对照受试者相比无显著差异。此外，MD组或AN组患者的ELF和血清中细胞因子表达水平之间未发现显著相关性。最后，在大多数MD患者ES标本的上皮细胞中检测到TNF-α、IL-6和IFN-γ的阳性表达，证实了这些细胞因子在MD患者ES中的表达上调。
本研究中ELF中TNF-α、IL-6和IFN-γ表达水平上调的鉴定为单侧MD患者ES微环境中免疫活性增加提供了直接证据，可能提示局部炎症反应是该疾病发病机制的基础。
