Highways to hell: Mechanism-based management of cytokine storm syndromes.
Highways to hell: Mechanism-based management of cytokine storm syndromes.
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DOI：
10.1016/j.jaci.2020.09.016
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Cron RQ
中科院分区：
文献类型：
--
作者：
Canna SW;Cron RQ
自2019年第一本专门介绍细胞因子风暴综合征（CSS）的教科书出版以来，世界发生了巨大变化，该术语的知名度也有所扩大。在此，我们将CSS广义地定义为包括危及生命/器官的全身性炎症和免疫病理学，而不管其发生的背景如何，认识到这种定义的模糊边界限制了其实用性。然而，我们专注于导致CSS的病理机制，包括颗粒介导的细胞毒性，特异性病毒感染，过量IL-18和嵌合抗原受体T细胞治疗的损害。这些机制通常反映在不同的临床特征、功能测试和/或生物标志物评估中。此外，这些机制往往表明具体的，明确的治疗。这种以机制为中心的组织对于推进该领域和理解个体患者的复杂性至关重要。然而，越来越多的证据表明，这些机制相互作用和重叠。同样地，广义术语如“细胞因子风暴”的效用在于，它反映了全身性炎症表型的趋同，无论原因或背景如何，其都可能适合于“炎症稳定化”。CSS研究必须提高我们对其各种机制及其相互作用和治疗的认识，但它还必须确定可能广泛预防CSS诱导的免疫病理学的迹象和干预措施。
Since the first textbook devoted to cytokine storm syndromes (CSSs) was published in 2019, the world has changed dramatically and the term’s visibility has broadened. Herein, we define CSSs broadly to include life/organ-threatening systemic inflammation and immunopathology regardless of the context in which it occurs, recognizing that the indistinct borders of such a definition limit its utility. Nevertheless, we are focused on the pathomechanisms leading to CSSs, including impairment of granule-mediated cytotoxicity, specific viral infections, excess IL-18, and chimeric antigen receptor T-cell therapy. These mechanisms are often reflected in distinct clinical features, functional tests, and/or biomarker assessments. Moreover, these mechanisms often indicate specific, definitive treatments. This mechanism-focused organization is vital to both advancing the field and understanding the complexities in individual patients. However, increasing evidence suggests that these mechanisms interact and overlap. Likewise, the utility of a broad term such as “cytokine storm” is that it reflects a convergence on a systemic inflammatory phenotype that, regardless of cause or context, may be amenable to “inflammo-stabilization.” CSS research must improve our appreciation of its various mechanisms and their interactions and treatments, but it must also identify the signs and interventions that may broadly prevent CSS-induced immunopathology.
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27.4
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