Ombrello Michael J, Schulert Grant S
Translational Genetics and Genomics Unit, Pediatric Translational Research Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland.
Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Transl Res. 2021 Jun;232:1-12. doi: 10.1016/j.trsl.2021.03.002. Epub 2021 Mar 5.
Although interest in "cytokine storms" has surged over the past decade, it was massively amplified in 2020 when it was suggested that a subset of patients with COVID-19 developed a form of cytokine storm. The concept of cytokine storm syndromes (CSS) encompasses diverse conditions or circumstances that coalesce around potentially lethal hyperinflammation with hemodynamic compromise and multiple organ dysfunction syndrome. Macrophage activation syndrome (MAS) is a prototypic form of CSS that develops in the context of rheumatic diseases, particularly systemic juvenile idiopathic arthritis. The treatment of MAS relies heavily upon corticosteroids and cytokine inhibitors, which have proven to be lifesaving therapies in MAS, as well as in other forms of CSS. Within months of the recognition of SARS-CoV2 as a human pathogen, descriptions of COVID-19 patients with hyperinflammation emerged. Physicians immediately grappled with identifying optimal therapeutic strategies for these patients, and despite clinical distinctions such as marked coagulopathy with endothelial injury associated with COVID-19, borrowed from the experiences with MAS and other CSS. Initial reports of patients treated with anti-cytokine agents in COVID-19 were promising, but recent large, better-controlled studies of these agents have had mixed results suggesting a more complex pathophysiology. Here, we discuss how the comparison of clinical features, immunologic parameters and therapeutic response data between MAS and hyperinflammation in COVID-19 can provide new insight into the pathophysiology of CSS.
尽管在过去十年中，人们对“细胞因子风暴”的兴趣激增，但在2020年，当有人提出一部分新冠肺炎患者会出现某种形式的细胞因子风暴时，这种兴趣大幅增加。细胞因子风暴综合征（CSS）的概念涵盖了各种情况，这些情况围绕着具有潜在致命性的过度炎症，伴有血流动力学障碍和多器官功能障碍综合征。巨噬细胞活化综合征（MAS）是CSS的一种典型形式，发生于风湿性疾病，尤其是系统性幼年特发性关节炎的背景下。MAS的治疗严重依赖于皮质类固醇和细胞因子抑制剂，这些已被证明在MAS以及其他形式的CSS中是挽救生命的疗法。在将严重急性呼吸综合征冠状病毒2（SARS-CoV2）识别为人类病原体后的几个月内，就出现了关于新冠肺炎炎症反应过度患者的描述。医生们立即着手为这些患者确定最佳治疗策略，尽管存在临床差异，如新冠肺炎相关的明显凝血病伴内皮损伤，但还是借鉴了MAS和其他CSS的经验。关于新冠肺炎患者接受抗细胞因子药物治疗的初步报告很有前景，但最近对这些药物进行的规模更大、控制更好的研究结果不一，这表明其病理生理学更为复杂。在此，我们讨论比较MAS与新冠肺炎炎症反应过度之间的临床特征、免疫参数和治疗反应数据，如何能够为CSS的病理生理学提供新的见解。
