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解析重症至危重症 COVID-19 患者的 IL-6/IL-10 细胞因子平衡。

Deciphering the balance of IL-6/IL-10 cytokines in severe to critical COVID-19 patients.

机构信息

Department of Immunology, Military Hospital of Tunis, Montfleury - 1008, Tunis, Tunisia; Unit IMEC-Immunology Microbiology Environmental and Carcinogenesis, Faculty of Science of Bizerte, Tunisia; Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia.

Unit IMEC-Immunology Microbiology Environmental and Carcinogenesis, Faculty of Science of Bizerte, Tunisia; Department of Biology, Faculty of Science of Gafsa, University of Gafsa, Gafsa, Tunisia.

出版信息

Immunobiology. 2022 Jul;227(4):152236. doi: 10.1016/j.imbio.2022.152236. Epub 2022 Jun 8.

Abstract

The severity of COVID-19 is largely determined by the inflammatory response, a "Cytokine storm," that involves both pro- and anti-inflammatory cytokines. In the current study we investigated the balance of pro- and anti-inflammatory status as represented by the levels of IL-6/IL-10 in severe to critical COVID-19 patients. 66 confirmed COVID-19 patients admitted to the ICU were categorized into groups according to the mortality and respiratory failure. Data were collected retrospectively in ICU, including a peripheral immune cells and infection-related biomarker CRP. The measurements of cytokine levels were performed by Immulite analyzer for IL-6 and ELISA sandwich for IL-10. In addition, longitudinal measurement of IL-6 was performed during 5 days post admission. Longitudinal assays showed that IL-6 was sustained at a medium level within 5 days post admission in severe cases who survived or not requiring mechanical ventilation, whereas it was sustained at high levels throughout the disease course in either deceased cases or who developed respiratory failure. The ratio of IL-6/lymphocytes was positively correlated with the risk of mortality, while IL-10/lymphocytes ratio could predict respiratory failure in ICU. IL-6/IL-10 profiling revealed that deceased patients have different magnitudes of both IL-6 and IL-10 cytokine release. Notably, excessive levels of IL-6 concomitant with high levels of IL-10 were more common in diseased COVID-19 patients. Taking into account the IL-6/IL-10 profiling may help clinicians to identify the right time of anti-inflammation treatment and select patients who will respond to anti-cytokine therapies and maintain an adequate inflammatory response for SARS-CoV-2 clearance.

摘要

COVID-19 的严重程度在很大程度上取决于炎症反应,即一种“细胞因子风暴”,涉及促炎和抗炎细胞因子。在本研究中,我们研究了 COVID-19 重症和危重症患者中代表促炎和抗炎状态平衡的 IL-6/IL-10 水平。66 名确诊 COVID-19 患者因 ICU 入住被分为根据死亡率和呼吸衰竭分组。数据在 ICU 中进行回顾性收集,包括外周免疫细胞和感染相关生物标志物 CRP。细胞因子水平的测量通过 Immulite 分析仪进行 IL-6 和 ELISA 夹心进行 IL-10。此外,在入院后 5 天内进行了 IL-6 的纵向测量。纵向检测表明,在需要机械通气或不需要机械通气的严重病例中,IL-6 在入院后 5 天内持续处于中等水平,而在死亡病例或发生呼吸衰竭的病例中,IL-6 持续处于高水平。IL-6/淋巴细胞比值与死亡率风险呈正相关,而 IL-10/淋巴细胞比值可预测 ICU 中的呼吸衰竭。IL-6/IL-10 分析显示,死亡患者的 IL-6 和 IL-10 细胞因子释放程度不同。值得注意的是,COVID-19 患者中过度的 IL-6 水平伴随着高水平的 IL-10 更为常见。考虑到 IL-6/IL-10 分析可能有助于临床医生确定抗炎治疗的正确时机,并选择对细胞因子治疗有反应并维持 SARS-CoV-2 清除所需的适当炎症反应的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b746/9173832/2c1d8f4f019d/gr1_lrg.jpg

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