Cytokine release syndrome (CRS) is known to be a factor in morbidity and mortality associated with acute viral infections including those caused by filoviruses and coronaviruses. IL-6 has been implicated as a cytokine negatively associated with survival after filovirus and coronavirus infection. However, IL-6 has also been shown to be an important mediator of innate immunity and important for the host response to an acute viral infection. Clinical studies are now being conducted by various researchers to evaluate the possible role of IL-6 blockers to improve outcomes in critically ill patients with CRS. Most of these studies involve the use of anti-IL-6R monoclonal antibodies (α-IL6R mAbs). We present data showing that direct neutralization of IL-6 with an α-IL-6 mAb in a BALB/c Ebolavirus (EBOV) challenge model produced a statistically significant improvement in outcome compared with controls when administered within the first 24 hours of challenge and repeated every 72 hours. A similar effect was seen in mice treated with the same dose of α-IL-6R mAb when the treatment was delayed 48 hrs post-challenge. These data suggest that direct neutralization of IL-6, early during the course of infection, may provide additional clinical benefits to IL-6 receptor blockade alone during treatment of patients with virus-induced CRS.

中文翻译：

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抗IL-6与抗IL-6R阻断抗体一起治疗BALB / c小鼠的急性埃博拉感染：治疗细胞因子释放综合征的潜在意义

细胞因子释放综合征（CRS）是与急性病毒感染（包括由丝状病毒和冠状病毒引起的病毒感染）相关的发病率和死亡率的一个因素。IL-6被认为是丝状病毒和冠状病毒感染后与存活负相关的细胞因子。但是，IL-6也被证明是先天免疫的重要介体，并且对于宿主对急性病毒感染的反应也很重要。现在，许多研究人员正在进行临床研究，以评估IL-6阻滞剂改善危重CRS患者预后的可能作用。这些研究大多数涉及抗IL-6R单克隆抗体（α-IL6RmAb）的使用。我们提供的数据显示，在挑战的前24小时内与对照组相比，在BALB / c埃博拉病毒（EBOV）挑战模型中用α-IL-6mAb直接中和IL-6的结果与对照组相比在统计学上有显着改善。每72小时重复一次。当攻击后48小时延迟治疗时，在用相同剂量的α-IL-6RmAb治疗的小鼠中观察到了类似的效果。这些数据表明，在感染过程的早期，直接中和IL-6可能会为病毒诱导的CRS患者治疗期间单独的IL-6受体阻断提供额外的临床益处。当攻击后48小时延迟治疗时，在用相同剂量的α-IL-6RmAb治疗的小鼠中观察到了类似的效果。这些数据表明，在感染过程的早期，直接中和IL-6可能会为病毒诱导的CRS患者治疗期间单独的IL-6受体阻断提供额外的临床益处。当攻击后48小时延迟治疗时，在用相同剂量的α-IL-6RmAb治疗的小鼠中观察到了类似的效果。这些数据表明，在感染过程中的早期就直接中和IL-6，可能在治疗病毒诱导的CRS患者期间单独为IL-6受体阻断提供额外的临床益处。