Khoshmirsafa Majid, Assarehzadegan Mohammad-Ali, Fallahpour Morteza, Azimi Maryam, Faraji Fatemeh, Riahi Taghi, Minaeian Sara, Fassahat Davood, Divsalar Farshad, Abbasi Mohammad Amin
Immunology Research Center, Institute of Immunology and Infectious Diseases; Iran University of Medical Sciences, Tehran, Iran.
Department of Immunology, School of Medicine; Iran University of Medical Sciences, Tehran, Iran.
Viral Immunol. 2022 Aug 23. doi: 10.1089/vim.2021.0224.
The purpose of this research was to investigate the gene expression levels of inflammatory cytokines interferon (IFN), tumor necrosis factor (TNF), interleukin (IL)1, IL2, IL6, IL8, and IL17, and anti-inflammatory cytokines IL4, IL10, IFN, and IFN, as well as relevant key transcription factors (TFs), including GATA3, PU1, NF-B (nuclear factor kappa-light-chain-enhancer of activated B cells), IRF3 (interferon regulatory factor 3), BCL6 (B cell lymphoma 6 protein), FOXP3 (forkhead box P3), RORt, and T-bet (T-box expressed in T cell) in Iranian patients with moderate and severe coronavirus disease 2019 (COVID-19). Fifty-six patients with COVID-19, and 25 healthy controls (HCs) age and sex matched were investigated. Based on the interim guidance of COVID-19 from the World Health Organization, the patients were classified into 33 moderate and 23 severe patients with COVID-19. The gene expression levels of cytokines and relevant TFs were quantified in peripheral blood mononuclear cells by quantitative real-time polymerase chain reaction (qRT-PCR). The gene expression levels of TFs RoR (RAR-related orphan nuclear receptor ), NF-B, and T-bet were significantly higher in patients with COVID-19 compared with HCs. Furthermore, the gene expression levels of cytokines, including IL2, IFN, IL6, TNF, IL1, IL8, and IL17, were significantly higher in patients with COVID-19 than HCs. However, there was a significant increase for IL6, TNF, and IL17 in severe compared with moderate patients with COVID-19. Finally, The Spearman correlation analysis revealed a significantly positive correlation for IL6 and TNF, IL6 and IL2, IL6, IFN, and IL2 and IFN. These data suggest that expression of IL6, TNF, and IL17 as well as the synergic effect of elevated values of IL2 and IFN should be considered in the treatment and management of patients with severe COVID-19.
本研究的目的是调查伊朗中度和重度2019冠状病毒病（COVID-19）患者中炎性细胞因子干扰素（IFN）、肿瘤坏死因子（TNF）、白细胞介素（IL）1、IL2、IL6、IL8和IL17以及抗炎细胞因子IL4、IL10、IFN和IFN的基因表达水平，以及相关关键转录因子（TFs），包括GATA3、PU1、核因子κB（NF-κB，活化B细胞的核因子κ轻链增强子）、干扰素调节因子3（IRF3）、B细胞淋巴瘤6蛋白（BCL6）、叉头框P3（FOXP3）、维甲酸相关孤儿核受体t（RORt）和T细胞表达的T盒（T-bet）。对56例COVID-19患者以及25例年龄和性别匹配的健康对照（HCs）进行了研究。根据世界卫生组织关于COVID-19的临时指南，将患者分为33例中度和23例重度COVID-19患者。通过定量实时聚合酶链反应（qRT-PCR）定量外周血单个核细胞中细胞因子和相关TFs的基因表达水平。与HCs相比，COVID-19患者中TFs RoR（维甲酸相关孤儿核受体）、NF-κB和T-bet的基因表达水平显著更高。此外，与HCs相比，COVID-19患者中细胞因子（包括IL2、IFN、IL6、TNF、IL1、IL8和IL17）的基因表达水平显著更高。然而，与中度COVID-19患者相比，重度患者中IL6、TNF和IL17显著升高。最后，Spearman相关性分析显示IL6与TNF、IL6与IL2、IL6、IFN以及IL2与IFN之间存在显著正相关。这些数据表明，在重度COVID-19患者的治疗和管理中应考虑IL6、TNF和IL17的表达以及IL2和IFN升高值的协同作用。
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