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眼内炎患者玻璃体中细胞因子水平升高可作为疾病严重程度的生物标志物。

Elevated cytokine levels in vitreous as biomarkers of disease severity in infectious endophthalmitis.

机构信息

Jhaveri Microbiology Centre, Brien Holden Eye Research Centre, L. V. Prasad Eye Institute, Hyderabad, Telangana, India.

Centre for Clinical Epidemiology and Biostatistics, L. V. Prasad Eye Institute, Hyderabad, India.

出版信息

PLoS One. 2018 Oct 8;13(10):e0205292. doi: 10.1371/journal.pone.0205292. eCollection 2018.

Abstract

PURPOSE

To investigate the immunopathogenesis of endophthalmitis, and determine if cytokine profiles could serve as biomarkers of disease severity in infectious endophthalmitis.

MATERIALS AND METHODS

Vitreous samples of 46 patients clinically diagnosed as endophthalmitis (of which 25 were culture positive) and 20 non-infectious controls from patients with Retinal Detachment (RD) or diabetic retinopathy were included in the study. The cytokine and chemokine expression patterns of 40 immune mediators including 6 antiinflammatory cytokines, 15 proinflammatory cytokines, 9 Growth factors and 10 proinflammatory chemokines in the vitreous were were analyzed by multiplex cytokine immunoassay. In addition, significant immune mediators were correlated with initial and final visual acuity (VA).

RESULTS

Our results demonstrated elevated expression of 16 mediators such as GCSF, GRO, IFN-γ, IL-1α, IL-1β, IL-1 RA, IL-6, IL-8, IP-10, MCP-1, MCP-3, MIP-1α, IL-1β, TGF-α, TNF-α in patients with culture positive endophthalmitis. Cytokine profile expression significantly differed between patients with proven endophthalmitis and the non-infectious controls in heat map analysis. PCoA plot indicated five mediators (IL-1RA, IL-6, IL-8, GRO, G-CSF) as biomarkers that could be Independent Predictors of Disease especially in culture negative cases. Correlation of cytokines with VA revealed strong association between the initial VA and intraocular levels of TGF-α, IL-1β and IL-8 but there was no correlation with the severity or visual outcome of infection.

CONCLUSION

In comparison to non-infectious ocular conditions, the pathogenesis of infectious endophthalmitis correlates with increased expression levels of IL-1RA, IL-6, IL-8, GRO, G-CSF. Understanding cytokine profiles in culture negative endophthalmitis patients could aid in therapy in non-responders to empirical antibiotic therapy.

摘要

目的

研究眼内炎的免疫发病机制,并确定细胞因子谱是否可作为感染性眼内炎疾病严重程度的生物标志物。

材料和方法

本研究纳入了 46 例临床诊断为眼内炎(其中 25 例培养阳性)和 20 例非感染性对照患者(来自视网膜脱离或糖尿病视网膜病变患者)的玻璃体样本。通过多重细胞因子免疫分析,分析了玻璃体中 40 种免疫介质(包括 6 种抗炎细胞因子、15 种促炎细胞因子、9 种生长因子和 10 种促炎趋化因子)的细胞因子和趋化因子表达模式。此外,还将显著的免疫介质与初始和最终视力(VA)相关联。

结果

我们的结果表明,在培养阳性眼内炎患者中,16 种介质(如 GCSF、GRO、IFN-γ、IL-1α、IL-1β、IL-1RA、IL-6、IL-8、IP-10、MCP-1、MCP-3、MIP-1α、IL-1β、TGF-α、TNF-α)的表达水平升高。热图分析表明,在培养阳性眼内炎患者和非感染性对照组之间,细胞因子谱表达存在显著差异。PCoA 图表明,五种介质(IL-1RA、IL-6、IL-8、GRO、G-CSF)作为生物标志物,可独立预测疾病,特别是在培养阴性病例中。细胞因子与 VA 的相关性表明,初始 VA 与眼内 TGF-α、IL-1β 和 IL-8 水平之间存在强烈关联,但与感染的严重程度或视觉结局无关。

结论

与非感染性眼部疾病相比,感染性眼内炎的发病机制与 IL-1RA、IL-6、IL-8、GRO、G-CSF 的表达水平升高有关。了解培养阴性眼内炎患者的细胞因子谱有助于辅助治疗对经验性抗生素治疗无反应的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1c7/6175518/95728185d75e/pone.0205292.g001.jpg

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