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Interleukin 6 (IL-6) is a cytokine with dual functions of pro-inflammation and anti-inflammation. It is mainly produced by mononuclear macrophages, Th2 cells, vascular endothelial cells and fibroblasts. IL-6 binds to glycoprotein 130 and one of these two receptors, membrane-bound IL-6R or soluble IL-6R, forming hexamer (IL-6/IL-6R/gp130), which then activates different signaling pathways (classical pathway, trans-signaling pathway) to exert dual immune-modulatory effects of anti-inflammation or pro-inflammation. Abnormal levels of IL-6 can cause multiple pathological reactions, including cytokine storm. Related clinical studies have found that IL-6 levels in severe COVID-19 patients were much higher than in healthy population. A large number of studies have shown that IL-6 can trigger a downstream cytokine storm in patients with COVID-19, resulting in lung damages, aggravating clinical symptoms and developing excessive inflammation and acute respiratory distress syndrome (ARDS). Monoclonal antibodies against IL-6 or IL-6R, such as tocilizumab, sarilumab, siltuximab and olokizumab may serve as therapeutic options for COVID-19 infection.


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What do we know about IL-6 in COVID-19 so far?

Show Author's information Jingrui Jiang1,2Jun Wang2,3Lulu Yao2,3Shenghan Lai4Xueji Zhang5( )
Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Department of Biomedicine and Biopharmacology, Hubei University of Technology, Wuhan 430068, China
National 111 Center for Cellular Regulation and Molecular Pharmaceutics, Wuhan 430068, China
Department of Pathology, Johns Hopkins University School of Medicine, MD 21287, USA
Guangdong Laboratory of Artificial Intelligence and Digital Economy (SZ), School of Biomedical Engineering, Shenzhen University, Shenzhen 518037, Guangdong, China

Abstract

Interleukin 6 (IL-6) is a cytokine with dual functions of pro-inflammation and anti-inflammation. It is mainly produced by mononuclear macrophages, Th2 cells, vascular endothelial cells and fibroblasts. IL-6 binds to glycoprotein 130 and one of these two receptors, membrane-bound IL-6R or soluble IL-6R, forming hexamer (IL-6/IL-6R/gp130), which then activates different signaling pathways (classical pathway, trans-signaling pathway) to exert dual immune-modulatory effects of anti-inflammation or pro-inflammation. Abnormal levels of IL-6 can cause multiple pathological reactions, including cytokine storm. Related clinical studies have found that IL-6 levels in severe COVID-19 patients were much higher than in healthy population. A large number of studies have shown that IL-6 can trigger a downstream cytokine storm in patients with COVID-19, resulting in lung damages, aggravating clinical symptoms and developing excessive inflammation and acute respiratory distress syndrome (ARDS). Monoclonal antibodies against IL-6 or IL-6R, such as tocilizumab, sarilumab, siltuximab and olokizumab may serve as therapeutic options for COVID-19 infection.

Keywords: COVID-19, Monoclonal antibody, IL-6, Cytokine storm, IL-6R

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Received: 08 July 2020
Accepted: 01 April 2021
Published: 07 July 2021
Issue date: June 2021

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