PDF(Pubmed)
Abstract：
Translational in vitro models such as cytokine release assay (CRA) are essential to assess the susceptibility to cytokine storm or CRS in a non-interventional manner in a human in vitro laboratory setting. Such models are also helpful to unravel disease mechanisms, to study the effects of new therapeutics and vaccines thereon and to diagnose or monitor diseases. Such assay will be important in predicting, planning and preparing for hospital intensive care units that are needed during the course of a pandemic. We present a CRA that can be adapted for assessing acute cytokine release risk against viral antigens, and potentially be used for cytokine storm simulation in viral infection outbreaks. We have used SARS-CoV-2 antigens and COVID-19 as a model. The assay can be challenged by changed or mutated forms of a virus in follow on waves of the epidemic and it can easily be modified for other future pandemics. We show that the membrane protein of SARS-CoV-2 is playing a major role in cytokine release (CR), mainly that of IL-6, IFNγ, TNFα and IL-8, that may be associated with COVID-19. These results are in agreement with recent clinical findings and new vaccine designs.
摘要：
翻译体外模型如细胞因子释放测定(CRA)对于在人体外实验室环境中以非介入方式评估对细胞因子风暴或CRS的易感性是必不可少的。这样的模型也有助于解开疾病机制，研究新疗法和疫苗的作用，并诊断或监测疾病。这样的测定将是重要的预测，规划和准备在大流行期间需要的医院重症监护病房。我们提出了一个CRA，可以适用于评估急性细胞因子释放风险针对病毒抗原，并可能用于病毒感染暴发中的细胞因子风暴模拟。我们使用SARS-CoV-2抗原和COVID-19作为模型。该测定可以通过在流行浪潮之后改变或突变形式的病毒来挑战，并且可以很容易地针对其他未来的大流行进行修改。我们表明SARS-CoV-2的膜蛋白在细胞因子释放（CR）中起主要作用，主要是IL-6，IFNγ，TNFα和IL-8，可能与COVID-19相关。这些结果与最近的临床发现和新的疫苗设计一致。
