Up-Regulated Expression of Interferon-Gamma, Interleukin-6 and Tumor Necrosis Factor-Alpha in the Endolymphatic Sac of Meniere's Disease Suggesting the Local Inflammatory Response Underlies the Mechanism of This Disease.

Chao Huang,Anquan Peng,Zhiwen Zhang,Wenqi Jiang,Xueying Pan,Li Huang,Wei Liu,Qin Wang,Wei Li

doi:10.3389/fneur.2022.781031

Abstract

BackgroundImmune 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.MethodsHuman 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.ResultsSignificant differences were identified in the expression levels of interferon-γ (IFN-γ) (P < 0.001), interleukin (IL)-6 (P = 0.008) and tumor necrosis factor-α (TNF-α) (P = 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.ConclusionsThe 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.

Highlights

Meniere’s disease (MD) is characterized by episodic vertigo, sensorineural hearing loss, and tinnitus or aural fullness
All cytokines were detected in samples of the diluted luminal fluid of the endolymphatic sac (ES), including the MD and acoustic neuroma (AN) groups, and the serum from the MD, AN and healthy groups
In samples of the diluted luminal fluid of the ES, no samples were identified that were above the maximum value in either the MD group or the AN group, whereas two samples from the AN group for IFN-γ, one sample from the MD group and two samples from the AN group for tumor necrosis factor-α (TNF-α), one sample from the MD group and two samples from the AN group for IL-17A, and one sample from the MD group and three samples from the AN group for IL-12p70, exhibited values below the detection limit

Summary

Introduction

Meniere’s disease (MD) is characterized by episodic vertigo, sensorineural hearing loss, and tinnitus or aural fullness. Previous studies have focused on the fact that the immune mediated inflammatory changes to the ES are associated with the production of EH in an animal model [7, 8], whereas the investigation of human ES in patients with MD revealed that mainly viral and autoimmune factors are involved in the pathological mechanism for MD [9–11]. As EH has been proposed to result from a disturbance in endolymphatic volume regulation that is associated with changes in the microenvironment of luminal fluid of the ES [12], understanding the molecular pathomechanism(s) underpinning the regulation of the immune reaction in the luminal fluids of ES is important both for furthering our knowledge of the physiopathology of EH and for identifying biomarkers for diagnosis or prognosis of pathologies of the MD. 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

Objectives

Results

Conclusion