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细胞因子谱在检测 COVID-19 住院患者严重肺部受累中的作用:IL-8/IL-32 轴。

Cytokine profiles in the detection of severe lung involvement in hospitalized patients with COVID-19: The IL-8/IL-32 axis.

机构信息

Department of Medical Sciences, Surgery and Neurosciences, Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Siena University, Siena, Italy.

Department of Medical Sciences, Surgery and Neurosciences, Respiratory Disease and Lung Transplant Unit, Respiratory Diseases and Transplant Unit, Siena University, Siena, Italy.

出版信息

Cytokine. 2022 Mar;151:155804. doi: 10.1016/j.cyto.2022.155804. Epub 2022 Jan 18.

Abstract

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disorder caused by a new coronavirus called SARS-CoV-2. The pathophysiology of severe COVID-19 is associated with a "cytokine storm". IL-32 is a key modulator in the pathogenesis of various clinical conditions and is mostly induced by IL-8. IL-32 modulates important inflammatory pathways (including TNF-α, IL-6 and IL-1b), contributing to the pathogenesis of inflammatory diseases. Il-32 was never evaluated before in COVID-19 patients stratifying as mild-moderate and severe patients. A total of 64 COVID-19 patients, 27 healthy controls were consecutively enrolled in the study. Serum concentrations of biomarkers including IL-1β, IL-10, IFN-γ, TNF-α and IL-6 were quantified by bead-based multiplex analysis and Serum concentration of IL-8 and IL-32 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, among the blood parameters, neutrophil and lymphocyte counts were significantly lower in severe COVID-19 patients than in the other, on the contrary, CRP was significantly higher in severe patients than in other groups. The cytokines that best distinguished controls from COVID-19 patients were IL-8 and IL-32, while IL-6 resulted the better variables for discriminate severe group. The best model performance for severe group was obtained by the combination of IL-32, IL-6, IFN-γ, and CRP serum concentration showing an AUC = 0.83. A cut off of 15 pg/ml of IL-6 greatly discriminate survivor from death patients. New insights related to the cytokine storm in COVID-19 patients, highlighting different severity of disease infection.

摘要

新型冠状病毒病(COVID-19)是一种由新型冠状病毒(SARS-CoV-2)引起的传染性呼吸系统疾病。重症 COVID-19 的病理生理学与“细胞因子风暴”有关。IL-32 是各种临床疾病发病机制中的关键调节剂,主要由 IL-8 诱导。IL-32 调节重要的炎症途径(包括 TNF-α、IL-6 和 IL-1b),导致炎症性疾病的发病机制。IL-32 在 COVID-19 患者中从未进行过评估,这些患者分为轻症-中度和重症患者。本研究连续纳入了 64 例 COVID-19 患者和 27 例健康对照者。采用基于珠的多重分析定量测定生物标志物(包括 IL-1β、IL-10、IFN-γ、TNF-α 和 IL-6)的血清浓度,采用酶联免疫吸附试验(ELISA)试剂盒测定血清 IL-8 和 IL-32 浓度。有趣的是,在血液参数中,重症 COVID-19 患者的中性粒细胞和淋巴细胞计数明显低于其他患者,相反,CRP 在重症患者中明显高于其他组。将健康对照者与 COVID-19 患者区分开来的最佳细胞因子是 IL-8 和 IL-32,而 IL-6 是区分重症组的更好变量。通过组合 IL-32、IL-6、IFN-γ 和 CRP 血清浓度,重症组获得了最佳的模型性能,AUC=0.83。IL-6 的截断值为 15pg/ml 时,可很好地区分存活者和死亡患者。COVID-19 患者细胞因子风暴的新见解,突出了疾病感染的不同严重程度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1024/8765080/ed01a4997212/gr1_lrg.jpg

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