Takashima Yasuo, Inaba Tohru, Matsuyama Tasuku, Yoshii Kengo, Tanaka Masami, Matsumoto Kazumichi, Sudo Kazuki, Tokuda Yuichi, Omi Natsue, Nakano Masakazu, Nakaya Takaaki, Fujita Naohisa, Sotozono Chie, Sawa Teiji, Tashiro Kei, Ohta Bon
Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Front Med (Lausanne). 2024 Feb 27;11:1319980. doi: 10.3389/fmed.2024.1319980. eCollection 2024.
In this study, we analyzed a relatively large subset of proteins, including 109 kinds of blood-circulating cytokines, and precisely described a cytokine storm in the expression level and the range of fluctuations during hospitalization for COVID-19. Of the proteins analyzed in COVID-19, approximately 70% were detected with Bonferroni-corrected significant differences in comparison with disease severity, clinical outcome, long-term hospitalization, and disease progression and recovery. Specifically, IP-10, sTNF-R1, sTNF-R2, sCD30, sCD163, HGF, SCYB16, IL-16, MIG, SDF-1, and fractalkine were found to be major components of the COVID-19 cytokine storm. Moreover, the 11 cytokines (i.e., SDF-1, SCYB16, sCD30, IL-11, IL-18, IL-8, IFN-γ, TNF-α, sTNF-R2, M-CSF, and I-309) were associated with the infection, mortality, disease progression and recovery, and long-term hospitalization. Increased expression of these cytokines could be explained in sequential pathways from hematopoietic progenitor cell differentiation to Th1-derived hyperinflammation in COVID-19, which might also develop a novel strategy for COVID-19 therapy with recombinant interleukins and anti-chemokine drugs.
在本研究中,我们分析了相对较大的蛋白质子集,包括109种血液循环细胞因子,并精确描述了新冠病毒疾病(COVID-19)住院期间细胞因子风暴在表达水平和波动范围方面的情况。在COVID-19中分析的蛋白质中,与疾病严重程度、临床结局、长期住院以及疾病进展和恢复相比,约70%的蛋白质经Bonferroni校正后存在显著差异。具体而言,发现IP-10、可溶性肿瘤坏死因子受体1(sTNF-R1)、可溶性肿瘤坏死因子受体2(sTNF-R2)、可溶性CD30(sCD30)、可溶性CD163(sCD163)、肝细胞生长因子(HGF)、趋化因子SCYB16、白细胞介素-16(IL-16)、γ干扰素诱导单核因子(MIG)、基质细胞衍生因子-1(SDF-1)和fractalkine是COVID-19细胞因子风暴的主要成分。此外,这11种细胞因子(即SDF-1、SCYB16、sCD30、白细胞介素-11(IL-11)、白细胞介素-18(IL-18)、白细胞介素-8(IL-8)、γ干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)、sTNF-R2、巨噬细胞集落刺激因子(M-CSF)和I-309)与感染、死亡率、疾病进展和恢复以及长期住院有关。这些细胞因子表达的增加可以在COVID-19中从造血祖细胞分化到Th1衍生的过度炎症的连续途径中得到解释,这也可能为使用重组白细胞介素和抗趋化因子药物治疗COVID-19开发一种新策略。