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A Comparative Assessment of Effects of Major Mediators of Acute Phase Response (IL-1, TNF-α, IL-6) on Breathing Pattern and Survival Rate in Rats with Acute Progressive Hypoxia
Journal of Evolutionary Biochemistry and Physiology ( IF 0.6 ) Pub Date : 2021-08-24 , DOI: 10.1134/s0022093021040177
Zh A Donina 1 , E V Baranova 1 , N P Aleksandrova 1
Affiliation  

Abstract

A pressing issue of the day is the identification of therapeutic targets to suppress the “cytokine storm” in COVID-19 complicated by acute respiratory distress syndrome (ARDS) with concomitant hypoxemia. However, the key cytokine and its relative contribution to the pathogenesis of ARDS, which leads to high mortality, are unknown. A comparative assessment of the effect of elevated systemic levels of pro-inflammatory cytokines IL-1β, TNF-1α and IL-6 on the respiratory patterns and survival rate in rats was carried out under progressively increasing acute hypoxia. Increasing hypoxia was simulated by a rebreathing method (from normoxia to apnea). The recorded parameters were the breathing pattern components (tidal volume and respiratory rate), minute ventilation (MV), oxygen saturation, apnea onset time, and posthypoxic survival rate. A comparative analysis was carried out under mild, moderate and severe hypoxia (at FIO2 = 15, 12 and 8%, respectively). It was shown that increasing hypoxia was accompanied by an acute suppression of the compensatory elevation of MV in rats with increased systemic levels of IL-1β and TNF-1α. By contrast, IL-6 caused an intensive elevation of MV with increasing hypoxia. Acute hypoxia (FIO2 < 8%), in all experimental series, was accompanied by an impairment of the respiratory rhythm up to the development of apnea. Posthypoxic breathing restoration (survival rate) was 50% with IL-1β and TNF-1α and only 10% with IL-6. The obtained results indicate that the elevated IL-6 level, despite the absence of respiratory disorders at the initial stage of the developing pathologic process, leads to a higher mortality in rats compared to IL-1β and TNF-1α. This allows considering IL-6 as an early prognostic biomarker of a high risk of mortality under severe hypoxemia.



中文翻译:

急性时相反应主要介质(IL-1、TNF-α、IL-6)对急性进行性缺氧大鼠呼吸模式和存活率影响的比较评估

摘要

当今的一个紧迫问题是确定治疗靶点,以抑制 COVID-19 并发急性呼吸窘迫综合征 (ARDS) 并伴有低氧血症的“细胞因子风暴”。然而,导致高死亡率的 ARDS 发病机制中的关键细胞因子及其相对贡献尚不清楚。在逐渐增加的急性缺氧条件下,比较评估促炎细胞因子 IL-1β、TNF-1α 和 IL-6 的全身水平升高对大鼠呼吸模式和存活率的影响。通过再呼吸方法(从常氧到呼吸暂停)模拟缺氧的增加。记录的参数是呼吸模式成分(潮气量和呼吸频率)、每分钟通气量 (MV)、氧饱和度、呼吸暂停发作时间和缺氧后存活率。I O 2分别为 15、12 和 8%)。结果表明,在全身 IL-1β 和 TNF-1α 水平升高的大鼠中,缺氧加剧伴随着 MV 代偿性升高的急性抑制。相比之下,IL-6 随着缺氧程度的增加导致 MV 的强烈升高。急性缺氧 (F I O 2< 8%),在所有实验系列中,伴随着呼吸节律的损害,直至出现呼吸暂停。IL-1β 和 TNF-1α 的缺氧后呼吸恢复(存活率)为 50%,IL-6 仅为 10%。获得的结果表明,与 IL-1β 和 TNF-1α 相比,尽管在发展的病理过程的初始阶段没有呼吸系统疾病,但升高的 IL-6 水平导致大鼠更高的死亡率。这允许将 IL-6 视为严重低氧血症下高死亡风险的早期预后生物标志物。

更新日期:2021-08-25
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