IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy?
IL-6 Inhibitors in the Treatment of Serious COVID-19: A Promising Therapy?
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DOI：
10.1007/s40290-020-00342-z
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发表时间：
2020-06-13
影响因子：
2.5
通讯作者：
Fatima, Zeenat
中科院分区：
文献类型：
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作者：
Atal, Shubham;Fatima, Zeenat
目前，尚无经证实的药物可用于治疗冠状病毒病（COVID-19）。现有证据不允许指南明确推荐临床试验范围外的任何药物。引起COVID-19的新型冠状病毒SARS-CoV-2引发了由多种细胞和介质（如白细胞介素（IL）-1，IL-6，IL-12和IL-18，肿瘤坏死因子α）驱动的高度炎症状态（TNF α）等。考虑到已证实的细胞因子失调在导致肺中的这种过度炎症中的作用，其中IL-6是关键驱动因素，特别是在重症COVID-19患者中，进一步探索用IL-6抑制剂tocilizumab、sar和siltuximab等药物进行选择性细胞因子阻断至关重要。这些靶向单克隆抗体可以抑制下游IL-6信号传导途径，这可能导致细胞增殖、分化、氧化应激、渗出减少，并改善具有明显的尼古丁驱动的炎症特征（如持续发热、呼吸困难和标志物升高）的患者的临床结局。tocilizumab的初步证据来自一些小型研究和随机对照试验的中期分析;后者也可用于sar。国际指南确实将IL-6抑制剂作为重症或危重症患者的选择之一。随着在不同国家注册和进行的一系列临床试验，对这些药物进行评估的兴趣越来越大。然而，调查的水平可能需要进一步加强，因为随着全球COVID-19死亡人数不断惊人地增加，有必要关注可以证明是“拯救生命”的治疗方案。随着更多证据的产生和大量系统研究的完成，IL-6抑制剂可能是一种这样的治疗选择。
At present, there are no proven agents for treatment of coronavirus disease (COVID-19). The available evidence has not allowed guidelines to clearly recommend any drugs outside the context of clinical trials. The novel coronavirus SARS-CoV-2 that causes COVID-19 invokes a hyperinflammatory state driven by multiple cells and mediators like interleukin (IL)-1, IL-6, IL-12, and IL-18, tumor necrosis factor alpha (TNF alpha), etc. Considering the proven role of cytokine dysregulation in causing this hyperinflammation in the lungs with IL-6 being a key driver, particularly in seriously ill COVID-19 patients, it is crucial to further explore selective cytokine blockade with drugs like the IL-6 inhibitors tocilizumab, sarilumab, and siltuximab. These targeted monoclonal antibodies can dampen the downstream IL-6 signaling pathways, which can lead to decreased cell proliferation, differentiation, oxidative stress, exudation, and improve clinical outcomes in patients with evident features of cytokine-driven inflammation like persistent fever, dyspnea and elevated markers. Preliminary evidence has come for tocilizumab from some small studies, and interim analysis of a randomized controlled trial; the latter also being available for sarilumab. International guidelines do include IL-6 inhibitors as one of the options available for severe or critically ill patients. There has been increased interest in evaluating these drugs with a series of clinical trials being registered and conducted in different countries. The level of investigation though perhaps needs to be further intensified as there is a need to focus on therapeutic options that can prove to be 'life-saving' as the number of COVID-19 fatalities worldwide keeps increasing alarmingly. IL-6 inhibitors could be one such treatment option, with generation of more evidence and completion of a larger number of systematic studies.