Cytokine Storm and Failed Resolution in COVID-19: Taking a Cue from Multiple Sclerosis.
Cytokine Storm and Failed Resolution in COVID-19: Taking a Cue from Multiple Sclerosis.
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DOI：
10.1007/978-3-030-85109-5_13
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发表时间：
2021
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过度的炎症反应和未能解决是多种疾病中组织损伤和器官功能障碍的主要常见原因，包括多发性硬化症（MS）、糖尿病和最近的COVID-19，尽管这些疾病的病因不同。促进炎症消退的自然过程长期以来被认为可以有效改善功能恢复和疾病结局。为了减轻MS中的过度炎症，科学研究确定了一组ω脂肪酸衍生物，被称为专门的促分解脂质介质（SPM），在治疗MS的临床前疾病模型中显着有效。本章基于我们对MS的观察。19感染诱导严重的细胞因子风暴，最终引发猖獗的炎症。感染和相关死亡率的影响在患有共病的患者中要高得多。此外，报告表明合理血糖控制的糖尿病患者结局更好，这无疑暗示了降糖药物（如二甲双胍）通过其抗炎特性在缓解疾病病理学方面的隐藏作用。值得注意的是，SPM和二甲双胍在人类患者中发挥广谱抗炎活性方面具有共同的治疗特征，具有上级安全性特征。当需要立即应对COVID-19的快速蔓延感染并控制导致严重器官损伤的病毒感染相关的病态炎症细胞因子风暴时，应认真考虑SPM和二甲双胍作为潜在的预防性治疗。鉴于目前对COVID-19的治疗仅为支持性治疗，全球研究旨在开发安全有效的治疗方案，从而改善合并症患者的临床病程。因此，从我们通过同时抑制炎症过程并刺激其消退来控制MS和糖尿病中的强烈炎症反应的经验中得到启示，二甲双胍和SPM在COVID-19中的组合疗法在治疗这一全球健康危机方面具有重大前景。
Excessive inflammatory responses and failed resolution are major common causes of tissue injury and organ dysfunction in a variety of diseases, including multiple sclerosis (MS), diabetes, and most recently, COVID-19, despite the distinct pathoetiology of the diseases. The promotion of the natural process of inflammatory resolution has been long recognized to improve functional recovery and disease outcomes effectively. To mitigate the excessive inflammation in MS, scientific investigations identified a group of derivatives of omega fatty acids, known as specialized pro-resolving lipid mediators (SPM) that have been significantly effective in treating preclinical disease models of MS. This chapter is based on our observations from MS. It is being increasingly deliberated that the ongoing COVID-19 infection induces severe cytokine storm that ultimately triggers rampant inflammation. The impact of infection and associated mortality is much higher in patients with co-morbid diseases. Also, reports suggest a better outcome in diabetic patients with reasonable glycemic control, which certainly hints towards a hidden role of anti-hyperglycemic drugs such as metformin in alleviating disease pathology through its anti-inflammatory feature. Notably, SPM and metformin share common therapeutic features in exerting a broad-spectrum anti-inflammatory activity in human patients with a superior safety profile. When there is an immediate need to encounter the fast-rampant infection of COVID-19 and control the viral-infection associated morbid inflammatory cytokine storm causing severe organ damage, SPM and metformin should be seriously considered as a potential adjunctive treatment. Given the fact that current treatment for COVID-19 is only supportive, global research is aimed at developing safe and effective therapeutic options that can result in a better clinical course in patients with comorbid conditions. Accordingly, taking a cue from our experiences in controlling robust inflammatory response in MS and diabetes by simultaneously inhibiting inflammatory process and stimulating its resolution, combinatorial therapy of metformin and SPM in COVID-19 holds significant promise in treating this global health crisis.