Division of Infectious Diseases, University of Colorado Denver Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora CO 80045, United States.
Division of Infectious Diseases, University of Colorado Denver Anschutz Medical Campus, 12700 E. 19th Avenue, Aurora CO 80045, United States.
Med Hypotheses. 2020 Nov;144:110053. doi: 10.1016/j.mehy.2020.110053. Epub 2020 Jun 27.
Interleukin-6 (IL-6) is a pleiotropic cytokine with effects in immune regulation, inflammation, and infection. The use of drugs that inhibit IL-6 biological activity has been proposed as a treatment for patients with Coronavirus Disease 2019 (COVID-19). The rationale for this approach includes commitment to the concept that inflammation is a cause of lung damage in COVID-19 and belief that IL-6 is a pro-inflammatory molecule. Observational data thought to support IL-6 inhibition include elevated circulating IL-6 levels in COVID-19 patients and association between elevated IL-6 and poor clinical outcomes. However, IL-6 has significant anti-inflammatory properties, which calls into question the rationale for employing IL-6 blockade to suppress inflammation-induced tissue injury. Also, studies suggesting a beneficial role for IL-6 in the host response to infection challenge the strategy of using IL-6 blockade to treat COVID-19. In studies of recombinant IL-6 injected into human volunteers, IL-6 levels exceeding those measured in COVID-19 patients have been observed with no pulmonary adverse events or other organ damage. These observations question the role of IL-6 as a contributing factor in COVID-19. Clinical experience with IL-6 receptor antagonists such as tocilizumab demonstrates increase in severe and opportunistic infections, raising concern about using tocilizumab and similar agents to treat COVID-19. Trials of drugs to inhibit IL-6 activity in COVID-19 are ongoing and will shed light on the role of IL-6 in COVID-19 pathogenesis. However, until more information is available, providers should exercise caution in prescribing these therapies given the potential for patient harm.
白细胞介素 6（IL-6）是一种具有免疫调节、炎症和感染作用的多效细胞因子。抑制 IL-6 生物活性的药物已被提议用于治疗 2019 年冠状病毒病（COVID-19）患者。这种方法的原理包括承诺炎症是 COVID-19 中肺损伤的原因，并且相信 IL-6 是一种促炎分子。被认为支持 IL-6 抑制的观察数据包括 COVID-19 患者循环中升高的 IL-6 水平以及升高的 IL-6 与不良临床结局之间的关联。然而，IL-6 具有显著的抗炎特性，这使得使用 IL-6 阻断来抑制炎症引起的组织损伤的原理受到质疑。此外，研究表明 IL-6 在宿主对感染的反应中具有有益作用，这挑战了使用 IL-6 阻断来治疗 COVID-19 的策略。在对人类志愿者注射重组 IL-6 的研究中，观察到 IL-6 水平超过 COVID-19 患者测量的水平，但没有肺部不良事件或其他器官损伤。这些观察结果质疑 IL-6 作为 COVID-19 发病机制的一个促成因素的作用。IL-6 受体拮抗剂（如托珠单抗）的临床经验表明严重和机会性感染增加，这引发了对使用托珠单抗和类似药物治疗 COVID-19 的担忧。正在进行 COVID-19 中抑制 IL-6 活性的药物试验，这将阐明 IL-6 在 COVID-19 发病机制中的作用。然而，在更多信息可用之前，鉴于患者可能受到伤害，提供者在开具这些治疗药物时应谨慎。
