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细胞因子风暴
Cytokine Storm


David C. Fajgenbaum ... 其他 • 2020.12.03
相关阅读
• 重症COVID-19 • tisagenlecleucel治疗儿童和年轻成人B细胞淋巴细胞白血病

严重急性呼吸综合征2型冠状病毒(SARS-CoV-2)大流行提醒我们,有效的宿主免疫应答发挥关键作用,而免疫失调会产生破坏性影响。今年距离首次描述嵌合抗原受体(CAR)T细胞疗法后的细胞因子风暴已有10年1,距离文献中首次使用细胞因子风暴一词描述异基因造血干细胞移植后的急性移植物抗宿主病这一移植综合征已有27年2。最初创建“细胞因子释放综合征”一词是为了描述输入muromonab-CD3(OKT3)之后的类似综合征3。细胞因子风暴和细胞因子释放综合征是危及生命的全身性炎症综合征,涉及循环系统内细胞因子水平升高和免疫细胞过度活化,其触发原因可以是各种治疗、病原体、癌症、自身免疫病和单基因病。

从历史角度来看,细胞因子风暴以前被认为是一种发生于全身性感染(如脓毒症)和免疫治疗(如Coley毒素)之后的流感样综合征4。鼠疫耶尔森菌感染(即鼠疫)以前曾引起大流行(如黑死病),并触发肺泡巨噬细胞产生过量细胞因子,造成细胞因子风暴5。过度免疫应答被怀疑是1918—1919年流感大流行的患者死因之一。事实上,与引起甲型流感的常见参考毒株相比,从1918年大流行分离出的一种重构H1N1病毒在小鼠中引发了明显的肺部炎症6。认识到引起多器官功能障碍的可能是对病原体的免疫应答,而非病原体本身,以及认识到类似的细胞因子风暴综合征可在无明显感染的情况下发生之后,我们开始研究免疫调节剂和细胞因子导向疗法。用于消除细胞因子风暴的最早靶向疗法之一是抗白介素-6受体单克隆抗体托珠单抗,它于20世纪90年代开发出来,用于治疗特发性多中心型卡斯尔曼病。还有多种其他疾病被认为是细胞因子风暴的原因,并被作为免疫导向疗法的靶点,如脓毒症、原发性和继发性噬血细胞性淋巴组织细胞增生症(HLH)、自身炎症性疾病和2019冠状病毒病(COVID-19)。





作者信息

David C. Fajgenbaum, M.D., and Carl H. June, M.D.
From the Department of Medicine, Division of Translational Medicine and Human Genetics, Center for Cytokine Storm Treatment and Laboratory (D.C.F.), and the Center for Cellular Immunotherapies and the Parker Institute for Cancer Immunotherapy (C.H.J.), Perelman School of Medicine, University of Pennsylvania, Philadelphia. Address reprint requests to Dr. Fajgenbaum at davidfa@pennmedicine.upenn.edu or to Dr. June at cjune@upenn.edu.

 

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