Aksu Muhammed D, van der Ent Tijmen, Zhang Zhenhua, Riza Anca L, de Nooijer Aline H, Ricaño-Ponce Isis, Janssen Nico, Engel Job J, Streata Ioana, Dijkstra Helga, Lemmers Heidi, Grondman Inge, Koeken Valerie A C M, Antoniadou Eleni, Antonakos Nikolaos, van de Veerdonk Frank L, Li Yang, Giamarellos-Bourboulis Evangelos J, Netea Mihai G, Ziogas Athanasios
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
J Infect. 2024 Dec;89(6):106300. doi: 10.1016/j.jinf.2024.106300. Epub 2024 Sep 30.
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.
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.
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.
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.
白细胞介素-1α/β（IL-1α/β）和肿瘤坏死因子（TNF）与重症新型冠状病毒肺炎（COVID-19）及脓毒症的病理过程密切相关。其受体的可溶性形式作为诱饵受体发挥作用，具有抑制效应。然而，关于它们在严重细菌和病毒感染中的调节机制知之甚少，本研究旨在对此进行探究。
对COVID-19患者、严重细菌感染患者和脓毒症患者血浆中的TNF循环可溶性受体（sTNFR1和sTNFR2）以及IL-1α/β循环可溶性受体（sIL-1R1、sIL-1R2）进行评估，并与健康对照者进行比较。此外，还在源自COVID-19或脓毒症患者的外周血单个核细胞（PBMC）中，在单细胞水平评估IL1R1、IL1R2、TNFRSF1A和TNFRSF1B的表达。
与健康受试者相比，COVID-19患者血浆中sIL-1R1、sTNFR1和sTNFR2的浓度显著更高。值得注意的是，ICU的COVID-19患者中sIL-1R1水平尤其升高，转录组分析表明重症COVID-19患者的PBMC中IL1R1表达增加。在严重细菌感染中，与健康对照相比，只有sTNFR1和sTNFR2水平升高。脓毒症患者的血浆sIL-1R1浓度降低，但与健康个体相比，sIL-1R2、sTNFR1和sTNFR2水平升高，这反映了脓毒症中单核细胞数量增加导致的表达升高。最后，脓毒症患者中sIL-1R2、sTNFR1和sTNFR2浓度升高与28天生存率降低呈中度相关。
我们的研究揭示了COVID-19和脓毒症中可溶性IL-1受体血浆浓度的不同调节机制。此外，可溶性TNF受体1和2在所有情况下均持续升高，且与脓毒症的疾病严重程度呈正相关。
