Interleukin-6 signaling blockade treatment for cytokine release syndrome in COVID-19 (Review)

Abstract

A severe immune response in patients with coronavirus disease 2019 (COVID-19) can cause a potentially lethal unconstrained inflammatory cytokine storm, known as cytokine release syndrome (CRS). The present study provides an overview of the biology underlying CRS and how targeted inhibition of interleukin (IL)-6 signaling may improve outcomes and the survival of patients suffering from COVID-19. Preliminary clinical results have indicated that antagonism of the IL-6 receptor (IL-6R), including with the FDA-approved humanized monoclonal antibody tocilizumab, can improve the outcomes of patients with severe or critical COVID-19 while maintaining a good safety profile. The available clinical data support the expansion of clinical trials using IL-6R targeting inhibitors for severe and critical COVID-19 treatment.

Keywords: Tocilizumab; clinical trials; coronavirus disease 2019; cytokine release syndrome; interleukin-6 signaling.

Figure 1

Actions of IL-6 and IL-6R inhibiting monoclonal antibodies on cytokine release-mediated inflammatory storms. The US FDA status of investigational drugs are shown with a green (approval) or red (rejection) box. The inhibitors suppress IL-6 signaling by impeding gp130 mediated activation of JAK and STAT3 signaling, thereby inhibiting cytokine-mediated inflammation and alleviating CRS. IL, interleukin; JAK, Janus kinase; sIL, soluble interleukin; glycoprotein 130, gp130.