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Persistent inflammation and T cell exhaustion in severe sepsis in the elderly

机译:老年人严重脓毒症的持续性炎症和T细胞衰竭

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IntroductionSepsis is known as a complex immunological response with hyperinflammation in the acute phase followed by immunosuppression. Although aging is crucial in sepsis, the impact of aging on inflammation and immunosuppression is still unclear. The purpose of this study was to investigate the relationship between inflammation and immunosuppression in aged patients and mice after sepsis.MethodsFifty-five patients with severe sepsis and 30 healthy donors were prospectively enrolled, and 90-day survival was compared between elderly (≥65?years) and adult (18–64 years) septic patients with serial measurement of serum interleukin (IL)-6. Within 24?h after diagnosis of severe sepsis, peripheral blood mononuclear cells were stimulated ex vivo to measure expression of the activation maker CD25 in T cells, IL-2 levels in the supernatant, and proliferation. In the mouse study, young (6–8 weeks) and aged (20–22 months) C57/B6 mice were subjected to cecal ligation and puncture (CLP), and survival was compared after 7?days with serial measurement of serum IL-6. Expression of the negative co-stimulatory molecules, CD25, and IL-2 in CD4+ T cells was measured.ResultsThe survival rate in elderly sepsis patients and aged septic mice was significantly lower than that in adult patients and young septic mice (60% vs. 93% in septic patients, 0% vs. 63% in septic mice, P?
机译:简介脓毒症是一种复杂的免疫反应,在急性期伴有高炎症,随后是免疫抑制。尽管衰老在脓毒症中至关重要,但衰老对炎症和免疫抑制的影响仍不清楚。方法探讨老年脓毒症和脓毒症小鼠的炎症反应与免疫抑制的关系。方法回顾性研究55例严重脓毒症患者和30名健康捐献者,比较老年人(≥65岁)的90天生存率。岁和成人(18-64岁)脓毒症患者,其血清白细胞介素(IL)-6含量连续测定。在诊断为严重脓毒症后的24小时内,离体刺激外周血单个核细胞,以测量T细胞中激活标记CD25的表达,上清液中IL-2的水平以及增殖。在小鼠研究中,对年轻(6-8周)和年龄较大(20-22个月)的C57 / B6小鼠进行盲肠结扎和穿刺(CLP),并在7天后对血清IL- 6。结果,老年败血症患者和老年败血症小鼠的存活率明显低于成年患者和年轻败血症小鼠的存活率(60%vs. 25%)。在败血病患者中为93%,在败血病小鼠中为0%,而在败血症小鼠中为63%(P <0.05)。老年败血症患者和老年败血症小鼠的血清IL-6水平持续高于成年患者和年轻败血症小鼠的血清IL-6水平。衰老小鼠的脾脏,淋巴结和外周血CD4 + T细胞中的负共刺激分子表达明显高于年轻小鼠(P <0.01)。与成年患者和年轻脓毒症小鼠相比,离体刺激在老年患者和老年败血症小鼠的CD4 + T细胞中降低了CD25表达,IL-2产生和增殖的程度。老年患者表现出败血症后14-16天和28-32天革兰氏阴性细菌检出率升高(P <0.05)。结论持续的炎症和T细胞衰竭可能与老年患者和败血症后小鼠的存活率下降有关。

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