COVID-19 患者血浆中 TNF 和 IL-1 可溶性受体的调节与败血症患者不同。

IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection Pub Date : 2024-09-30 DOI:10.1016/j.jinf.2024.106300

Muhammed D. Aksu , Tijmen van der Ent , Zhenhua Zhang , Anca L. Riza , Aline H. de Nooijer , Isis Ricaño-Ponce , Nico Janssen , Job J. Engel , Ioana Streata , Helga Dijkstra , Heidi Lemmers , Inge Grondman , Valerie A.C.M. Koeken , Eleni Antoniadou , Nikolaos Antonakos , Frank L. van de Veerdonk , Yang Li , Evangelos J. Giamarellos-Bourboulis , Mihai G. Netea , Athanasios Ziogas

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引用次数: 0

摘要

目的：IL-1α/β 和 TNF 与严重 COVID-19 和败血症的病理学密切相关。它们的可溶性受体作为诱饵受体，具有抑制作用。然而，我们对它们在严重细菌和病毒感染中的调节作用知之甚少，本研究旨在对此进行研究：方法：评估 COVID-19、严重细菌感染和败血症患者血浆中 TNF（sTNFR1 和 sTNFR2）和 IL-1α/β （sIL-1R1、sIL-1R2）的循环可溶性受体，并与健康对照组进行比较。此外，还在 COVID-19 或败血症患者的 PBMCs 中评估了 IL1R1、IL1R2、TNFRSF1A 和 TNFRSF1B 在单细胞水平上的表达：结果：与健康人相比，COVID-19 患者血浆中 sIL-1R1、sTNFR1 和 sTNFR2 的浓度明显较高。值得注意的是，ICU COVID-19 患者的 sIL-1R1 水平特别高，转录组分析表明严重 COVID-19 患者的 PBMCs 中 IL1R1 表达增强。在严重细菌感染中，与健康对照组相比，只有 sTNFR1 和 sTNFR2 的水平有所升高。与健康人相比，败血症患者血浆中的 sIL-1R1 浓度降低，但 sIL-1R2、sTNFR1 和 sTNFR2 水平升高，这反映了败血症中单核细胞数量增加导致表达增强。最后，sIL-1R2、sTNFR1 和 sTNFR2 浓度的升高与败血症患者 28 天存活率的降低呈中度相关：我们的研究揭示了 COVID-19 和脓毒症患者血浆中可溶性 IL-1 受体浓度的不同调节方式。此外，可溶性 TNF 受体 1 和 2 在所有情况下均持续上升，并与败血症的疾病严重程度呈正相关。

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Regulation of plasma soluble receptors of TNF and IL-1 in patients with COVID-19 differs from that observed in sepsis

Objectives

IL-1α/β and TNF are closely linked to the pathology of severe COVID-19 and sepsis. The soluble forms of their receptors, functioning as decoy receptors, exhibit inhibitory effects. However, little is known about their regulation in severe bacterial and viral infections, which we aimed to investigate in this study.

Methods

The circulating soluble receptors of TNF (sTNFR1 and sTNFR2) and IL-1α/β (sIL-1R1, sIL-1R2) were evaluated in the plasma of patients with COVID-19, severe bacterial infections, and sepsis and compared with healthy controls. Additionally, IL1R1, IL1R2, TNFRSF1A, and TNFRSF1B expression was evaluated at the single cell level in PBMCs derived from COVID-19 or sepsis patients.

Results

Plasma concentrations of sIL-1R1, sTNFR1, and sTNFR2 were significantly higher in COVID-19 patients compared to healthy subjects. Notably, sIL-1R1 levels were particularly elevated in ICU COVID-19 patients, and transcriptome analysis indicated heightened IL1R1 expression in PBMCs from severe COVID-19 patients. In severe bacterial infections, only sTNFR1 and sTNFR2 exhibited increased levels compared to healthy controls. Sepsis patients had decreased sIL-1R1 plasma concentrations but elevated sIL-1R2, sTNFR1, and sTNFR2 levels compared to healthy individuals, reflecting the heightened expression due to the increased numbers of monocytes present in sepsis. Finally, elevated concentrations of sIL-1R2, sTNFR1, and sTNFR2 were moderately associated with reduced 28-day survival in sepsis patients.

Conclusion

Our study reveals distinct regulation of plasma concentrations of soluble IL-1 receptors in COVID-19 and sepsis. Moreover, soluble TNF receptors 1 and 2 consistently rise in all conditions and show a positive correlation with disease severity in sepsis.

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来源期刊

Journal of Infection 医学-传染病学

CiteScore

45.90

自引率

3.20%

发文量

475

审稿时长

16 days

期刊介绍： The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.