Biava Mirella, Notari Stefania, Grassi Germana, Bordi Licia, Tartaglia Eleonora, Agrati Chiara, Cimini Eleonora, Sberna Giuseppe, Nicastri Emanuele, Antinori Andrea, Girardi Enrico, Vaia Francesco, Maggi Fabrizio, Lalle Eleonora
Laboratory of Virology and Biosafety Laboratories, National Institute of Infectious Diseases "L. Spallanzani", IRCCS, 00149 Rome, Italy.
Cellular Immunology Laboratory, National Institute of Infectious Diseases "L. Spallanzani", IRCCS, 00149 Rome, Italy.
Microorganisms. 2023 Nov 16;11(11):2787. doi: 10.3390/microorganisms11112787.
COVID-19 patients show characteristic over-expression of different cytokines that may interfere with the interferon (IFN) response, delaying its production. Within the overexpressed cytokines, IL-8 plays a key role, and it may impede IFN-I activation. PBMC from eight healthy donors were exposed to 2019-nCoV/Italy-INMI1 isolate and supernatants/cells were collected at different time points; the production of either IFN-alpha or IL-8 was assessed. The same analysis was performed on plasma samples obtained from 87 COVID-19 patients. Antagonism between IFN-alpha and IL-8 was observed, since in those PBMC with medium or high IL-8 levels, IFN-α levels were low. The same scenario was observed in SARS-CoV-2-infected patients that were divided into three groups based on IL-8 low, medium and high levels; the correlation between low levels of IFN-α and high levels of IL-8 was statistically significant in both the IL-8 medium and IL-8 high group. Overall, our results showed a crosstalk/antagonism between IL-8 and IFN-alpha in PBMC from healthy donors challenged with SARS-CoV-2 and inversely proportional IFN-alpha levels to IL-8 concentrations detected in plasma samples from COVID-19 patients, suggesting that the impairment of the innate immune response in COVID-19 patients may be linked to a dysregulated cytokine response, namely through IL-8 production.
新冠肺炎患者表现出不同细胞因子的特征性过表达,这些细胞因子可能会干扰干扰素(IFN)反应,延迟其产生。在过表达的细胞因子中,白细胞介素-8(IL-8)起关键作用,它可能会阻碍I型干扰素(IFN-I)的激活。来自8名健康供体的外周血单个核细胞(PBMC)暴露于2019-nCoV/Italy-INMI1毒株,并在不同时间点收集上清液/细胞;评估干扰素-α(IFN-α)或IL-8的产生。对从87例新冠肺炎患者获得的血浆样本进行了同样的分析。观察到IFN-α和IL-8之间存在拮抗作用,因为在那些IL-8水平为中或高的PBMC中,IFN-α水平较低。在根据IL-8水平分为低、中、高三组的新冠病毒2(SARS-CoV-2)感染患者中也观察到了同样的情况;在IL-8中等水平组和IL-8高水平组中,低水平的IFN-α与高水平的IL-8之间的相关性均具有统计学意义。总体而言,我们的结果表明,在受到SARS-CoV-2攻击的健康供体的PBMC中,IL-8和IFN-α之间存在相互作用/拮抗作用,且在新冠肺炎患者血浆样本中检测到的IFN-α水平与IL-8浓度成反比,这表明新冠肺炎患者先天免疫反应的损害可能与细胞因子反应失调有关,即通过IL-8的产生。