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嗜酸性中耳炎积液中嗜酸性粒细胞衍生神经毒素、弹性蛋白酶及细胞因子谱

Eosinophil-derived neurotoxin, elastase, and cytokine profile in effusion from eosinophilic otitis media.

作者信息

Uchimizu Hirotaka, Matsuwaki Yoshinori, Kato Masahiko, Otori Nobuyosi, Kojima Hiromi

机构信息

Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan.

Department of Otorhinolaryngology, The Jikei University School of Medicine, Tokyo, Japan.

出版信息

Allergol Int. 2015 Sep;64 Suppl:S18-23. doi: 10.1016/j.alit.2015.03.007. Epub 2015 Apr 25.

Abstract

BACKGROUND

Eosinophilic otitis media (EOM) is an intractable disease characterized by a remarkably viscous effusion and accumulation of numerous eosinophils in both the middle ear effusion and the mucosa. The key factors in EOM pathogenesis remain unclear. The purpose of this study is to identify the important factors involved in EOM pathogenesis.

METHODS

Middle ear effusion samples were collected from 12 patients with EOM and 9 patients with secretory otitis media (SOM), as controls. Multiple cytokines in the effusion were measured using a Bio-Plex™ Human Cytokine 27-Plex panel. Eosinophil-derived neurotoxin (EDN) and elastase were measured by ELISA. The concentrations of EDN, elastase, and each cytokine were compared between the EOM and SOM groups. Furthermore, in the EOM group, each cytokine was examined for correlation with EDN and elastase.

RESULTS

EDN and elastase concentrations were significantly higher in the EOM group than in the SOM group (p < 0.05). IL-5, IL-1β, MIP-1α, G-CSF, IL-1ra, IL-4, IFN-γ, MIP-1β, IL-10, TNF-α, VEGF, and IL-2 concentration was significantly higher in the EOM group than in the SOM group (p < 0.05). Significant positive correlations were found between EDN and IL-1ra, IL-2, IL-5, IL-9, IL-13, eotaxin, MIP-1α, PDGF-BB, and RANTES in the EOM group (p < 0.05).

CONCLUSIONS

Our study showed that IL-5, IL-2, MIP-1α, and IL-1ra are the important factors involved in EOM pathogenesis. Furthermore, not only eosinophil, but also neutrophil are involved in middle ear inflammation of EOM.

摘要

背景

嗜酸性粒细胞性中耳炎(EOM)是一种难治性疾病,其特征为中耳积液显著黏稠,且中耳积液和黏膜中有大量嗜酸性粒细胞积聚。EOM发病机制中的关键因素仍不清楚。本研究的目的是确定参与EOM发病机制的重要因素。

方法

收集12例EOM患者和9例分泌性中耳炎(SOM)患者的中耳积液样本作为对照。使用Bio-Plex™人细胞因子27项检测板测定积液中的多种细胞因子。通过酶联免疫吸附测定法检测嗜酸性粒细胞衍生神经毒素(EDN)和弹性蛋白酶。比较EOM组和SOM组中EDN、弹性蛋白酶及每种细胞因子的浓度。此外,在EOM组中,检测每种细胞因子与EDN和弹性蛋白酶的相关性。

结果

EOM组中EDN和弹性蛋白酶浓度显著高于SOM组(p < 0.05)。EOM组中白细胞介素-5(IL-5)、白细胞介素-1β(IL-1β)、巨噬细胞炎性蛋白-1α(MIP-1α)、粒细胞集落刺激因子(G-CSF)、白细胞介素-1受体拮抗剂(IL-1ra)、白细胞介素-4(IL-4)、干扰素-γ(IFN-γ)、巨噬细胞炎性蛋白-1β(MIP-1β)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、血管内皮生长因子(VEGF)和白细胞介素-2(IL-2)浓度显著高于SOM组(p < 0.05)。在EOM组中,EDN与IL-1ra、IL-2、IL-5、IL-9、IL-13、嗜酸性粒细胞趋化因子、MIP-1α、血小板衍生生长因子-BB(PDGF-BB)和调节激活正常T细胞表达和分泌因子(RANTES)之间存在显著正相关(p < 0.05)。

结论

我们的研究表明,IL-5、IL-2、MIP-1α和IL-1ra是参与EOM发病机制的重要因素。此外,不仅嗜酸性粒细胞,中性粒细胞也参与了EOM的中耳炎症。

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