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循环细胞因子的特定模式和动态与哥伦比亚成年 COVID-19 患者肺损伤和死亡率的延长有关。

A Specific Pattern and Dynamics of Circulating Cytokines Are Associated with the Extension of Lung Injury and Mortality in Colombian Adults with Coronavirus Disease-19.

机构信息

Programa de Medicina, División de Inmunología; Universidad Surcolombiana, Neiva, Huila, Colombia.

Servicio de Neumología, E.S.E. Hospital Universitario de Neiva, Neiva, Huila, Colombia.

出版信息

J Interferon Cytokine Res. 2023 May;43(5):206-215. doi: 10.1089/jir.2023.0001. Epub 2023 Apr 27.

Abstract

Increased systemic levels of inflammatory cytokines have been associated with the development of pathophysiologic events during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To further explore differences in the pattern and dynamics of plasma cytokines in individuals with coronavirus disease-19 (COVID-19), and the relationship with disease mortality, here we evaluated the plasma levels of proinflammatory and regulatory cytokines in Colombian patient survivors and nonsurvivors of SARS-CoV-2 infection. Individuals with confirmed COVID-19, with other respiratory diseases requiring hospitalization, and healthy controls, were included. Plasma levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon-γ, IL-10, soluble tumor necrosis factor receptor I (sTNFRI), and transforming growth factor-β1 were measured by a bead-based assay or enzyme-linked immunosorbent assay and clinical, laboratory, and tomographic parameters were registered during hospitalization. The levels of most of the evaluated cytokines were increased in COVID-19 individuals relative to healthy controls. The levels of IL-6, IL-10, and sTNFRI were directly associated with the development of respiratory failure, immune dysregulation, and coagulopathy, as well as with COVID-19 mortality. Particularly, the early, robust, and persistent increase of circulating IL-6 characterized COVID-19 nonsurvivors, while survivors were able to counteract the inflammatory cytokine response. In addition, IL-6 systemic levels positively correlated with the tomographic extension of lung damage in individuals with COVID-19. Thus, an exacerbated inflammatory cytokine response, particularly mediated by IL-6 added to the inefficiency of regulatory cytokines, distinguishes COVID-19-associated tissue disturbances, severity, and mortality in Colombian adults.

摘要

在严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染期间,全身性炎症细胞因子水平升高与病理生理事件的发展有关。为了进一步探讨 2019 冠状病毒病 (COVID-19) 患者血浆细胞因子模式和动态的差异及其与疾病死亡率的关系,我们评估了哥伦比亚 SARS-CoV-2 感染患者幸存者和非幸存者的血浆促炎和调节细胞因子水平。纳入了确诊为 COVID-19 的患者、需要住院治疗的其他呼吸道疾病患者和健康对照者。通过基于珠的测定或酶联免疫吸附测定测量了白细胞介素 (IL)-6、肿瘤坏死因子 (TNF)-α、干扰素-γ、IL-10、可溶性肿瘤坏死因子受体 I (sTNFRI) 和转化生长因子-β1 的血浆水平,并在住院期间记录了临床、实验室和断层扫描参数。与健康对照组相比,COVID-19 患者大多数评估细胞因子的水平升高。IL-6、IL-10 和 sTNFRI 的水平与呼吸衰竭、免疫失调和凝血功能障碍的发展以及 COVID-19 死亡率直接相关。特别是,循环 IL-6 的早期、强烈和持续增加是 COVID-19 非幸存者的特征,而幸存者能够对抗炎症细胞因子反应。此外,IL-6 全身水平与 COVID-19 个体肺部损伤的断层扫描扩展呈正相关。因此,炎症细胞因子反应的加剧,特别是由 IL-6 介导的炎症细胞因子反应的加剧,加上调节细胞因子的效率低下,区分了哥伦比亚成年人中与 COVID-19 相关的组织紊乱、严重程度和死亡率。

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