Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, 17. Vas str., Budapest, 1088, Hungary.
I. Department of Internal Medicine and Gastroenterology, Department of Orthopaedics - COVID Quarantine, ÉKC New Saint John's Hospital, 1-3. Diós árok, Budapest, 1125, Hungary.
Cell Commun Signal. 2021 Jan 13;19(1):7. doi: 10.1186/s12964-020-00699-3.
The cytokine release syndrome or cytokine storm, which is the hyper-induction of inflammatory responses has a central role in the mortality rate of COVID-19 and some other viral infections. Interleukin-6 (IL-6) is a key player in the development of cytokine storms. Shedding of interleukin-6 receptor (IL-6Rα) results in the accumulation of soluble interleukin-6 receptors (sIL-6R). Only relatively few cells express membrane-bound IL-6Rα. However, sIL-6R can act on potentially all cells and organs through the ubiquitously expressed gp130, the coreceptor of IL-6Rα. Through this, so-called trans-signaling, IL-6-sIL-6R is a powerful factor in the development of cytokine storms and multiorgan involvement. Some bacteria (e.g., Serratia marcescens, Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes), commonly considered to cause co-infections during viral pneumonia, can directly induce the shedding of membrane receptors, including IL-6Rα, or enhance endogenous shedding mechanisms causing the increase of sIL-6R level. Here we hypothesise that bacteria promoting shedding and increase the sIL-6R level can be an important contributing factor for the development of cytokine storms. Therefore, inhibition of IL-6Rα shedding by drastically reducing the number of relevant bacteria may be a critical element in reducing the chance of a cytokine storm. Validation of this hypothesis can support the consideration of the prophylactic use of antibiotics more widely and at an earlier stage of infection to decrease the mortality rate of COVID-19. Video abstract.
细胞因子释放综合征或细胞因子风暴，即炎症反应的过度诱导，在 COVID-19 和一些其他病毒感染的死亡率中起着核心作用。白细胞介素 6（IL-6）是细胞因子风暴发展的关键因素。白细胞介素 6 受体（IL-6Rα）的脱落导致可溶性白细胞介素 6 受体（sIL-6R）的积累。只有相对较少的细胞表达膜结合的 IL-6Rα。然而，sIL-6R 可以通过普遍表达的 gp130（IL-6Rα 的核心受体）作用于潜在的所有细胞和器官。通过这种所谓的转信号，IL-6-sIL-6R 是细胞因子风暴和多器官受累发展的有力因素。一些细菌（例如粘质沙雷氏菌、金黄色葡萄球菌、铜绿假单胞菌、李斯特菌单核细胞增生症），通常被认为在病毒性肺炎期间会引起合并感染，可直接诱导膜受体（包括 IL-6Rα）脱落，或增强内源性脱落机制导致 sIL-6R 水平升高。在这里，我们假设促进脱落和增加 sIL-6R 水平的细菌可能是细胞因子风暴发展的一个重要因素。因此，通过大大减少相关细菌的数量来抑制 IL-6Rα 的脱落可能是降低细胞因子风暴机会的关键因素。验证这一假设可以支持更广泛地考虑预防性使用抗生素，并在感染的早期阶段使用抗生素，以降低 COVID-19 的死亡率。视频摘要。
