Immunology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
Department of Cardiac Pathology, Health Research Institute of the Principality of Asturias - ISPA, Oviedo, Spain.
Front Immunol. 2021 Aug 12;12:687582. doi: 10.3389/fimmu.2021.687582. eCollection 2021.
High levels of inflammation play an important role in chronic heart failure (CHF). Patients with CHF have elevated levels of pro-inflammatory cytokines circulating systemically, mainly TNF and IL-6. However, there are almost no studies that relate these levels to the functional status of patients in CHF, much less to their CMV serostatus. In this study, patients with CHF (n=40; age=54.9 ± 6.3; New York Heart Association functional classification (NYHA, I-III) and healthy controls (n=40; age=53.5 ± 7.1) were analyzed. The serum concentrations of nine pro- and anti-inflammatory cytokines were measured by Luminex xMap Technology and the basal level of mRNA expression of some immune molecules was quantified by TaqMan™ Array in CD4+ T-lymphocytes. The concentration of these cytokines in culture supernatants in response to anti-CD3 and LPS was also measured. The percentage of CD28null T-cells was determined, as well as the antibody titer against CMV. We found a higher concentration of all cytokines studied in CHF serum compared to healthy controls, as well as a direct correlation between functional status in CHF patients and levels of inflammatory cytokines. Moreover, the highest cytokine concentrations were found in patients with higher concentrations of lymphocytes lacking CD28 molecule. The cytokine production was much higher in CMV+ patients, and the production of these cytokines was found mainly in the T-lymphocytes of CMV+ patients in response to anti-CD3. Anti-CMV antibody levels were positively correlated with cytokine levels. The baseline expression of specific mRNA of the main molecules involved in the Th1 response, as well as molecules related to the CD4+CD28 null subset was higher in CMV+ patients. The cytokine concentrations are higher in CHF CMV+ patients and these concentrations are related to the production of antibodies against CMV. These high levels of cytokines are also associated with the more differentiated CD28null lymphocyte populations. All this, together with the dynamics of the pathology itself, makes CMV+ patients present a worse functional status and possibly a worse evolution of the pathology.
高水平的炎症在慢性心力衰竭（CHF）中起着重要作用。CHF 患者体内循环系统中促炎细胞因子水平升高，主要是 TNF 和 IL-6。然而，几乎没有研究将这些水平与 CHF 患者的功能状态相关联，更不用说与他们的 CMV 血清状态相关联了。在这项研究中，分析了 CHF 患者（n=40；年龄=54.9±6.3；纽约心脏协会功能分类（NYHA，I-III）和健康对照组（n=40；年龄=53.5±7.1）。通过 Luminex xMap 技术测量了 9 种促炎和抗炎细胞因子的血清浓度，并通过 TaqMan™Array 定量测定了 CD4+T 淋巴细胞中一些免疫分子的基础 mRNA 表达水平。还测量了这些细胞因子在培养上清液中对抗 CD3 和 LPS 的反应。测定了 CD28null T 细胞的百分比以及针对 CMV 的抗体滴度。与健康对照组相比，我们发现 CHF 血清中所有研究细胞因子的浓度都更高，并且 CHF 患者的功能状态与炎症细胞因子的水平直接相关。此外，在 CD28 分子缺失的淋巴细胞浓度较高的患者中发现了最高的细胞因子浓度。CMV+患者的细胞因子产生量更高，并且这些细胞因子的产生主要发生在 CMV+患者的 T 淋巴细胞中，以响应抗 CD3。抗 CMV 抗体水平与细胞因子水平呈正相关。CMV+患者中主要涉及 Th1 反应的主要分子以及与 CD4+CD28null 亚群相关的分子的特定 mRNA 的基础表达更高。CMV+CHF 患者的细胞因子浓度较高，这些浓度与针对 CMV 的抗体产生有关。这些高水平的细胞因子也与更分化的 CD28null 淋巴细胞群体有关。所有这些，连同病理学本身的动态变化，使得 CMV+患者表现出更差的功能状态和可能更差的病理学演变。
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