Anti-IL-6 Versus Anti-IL-6R Blocking Antibodies to Treat Acute Ebola Infection in BALB/c Mice: Potential Implications for Treating Cytokine Release Syndrome

Reid Rubsamen; Scott Burkholz; Christopher Massey; Trevor Brasel; Tom Hodge; Lu Wang; Charles Herst; Richard Carback; Paul Harris

doi:10.3389/fphar.2020.574703

Anti-IL-6 Versus Anti-IL-6R Blocking Antibodies to Treat Acute Ebola Infection in BALB/c Mice: Potential Implications for Treating Cytokine Release Syndrome

Front Pharmacol. 2020 Sep 23:11:574703. doi: 10.3389/fphar.2020.574703. eCollection 2020.

Authors

Reid Rubsamen^{1

2}, Scott Burkholz¹, Christopher Massey³, Trevor Brasel³, Tom Hodge¹, Lu Wang¹, Charles Herst¹, Richard Carback¹, Paul Harris⁴

Affiliations

¹ Flow Pharma Inc., Pleasant Hill, CA, United States.
² Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States.
³ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, United States.
⁴ Department of Medicine, Columbia University, New York, NY, United States.

Abstract

Cytokine release syndrome (CRS) is known to be a factor in morbidity and mortality associated with acute viral infections including those caused by filoviruses and coronaviruses. IL-6 has been implicated as a cytokine negatively associated with survival after filovirus and coronavirus infection. However, IL-6 has also been shown to be an important mediator of innate immunity and important for the host response to an acute viral infection. Clinical studies are now being conducted by various researchers to evaluate the possible role of IL-6 blockers to improve outcomes in critically ill patients with CRS. Most of these studies involve the use of anti-IL-6R monoclonal antibodies (α-IL-6R mAbs). We present data showing that direct neutralization of IL-6 with an α-IL-6 mAb in a BALB/c Ebolavirus (EBOV) challenge model produced a statistically significant improvement in outcome compared with controls when administered within the first 24 h of challenge and repeated every 72 h. A similar effect was seen in mice treated with the same dose of α-IL-6R mAb when the treatment was delayed 48 h post-challenge. These data suggest that direct neutralization of IL-6, early during the course of infection, may provide additional clinical benefits to IL-6 receptor blockade alone during treatment of patients with virus-induced CRS.

Keywords: Anti-IL-6; Anti-IL-6R; COVID-19; Ebola (EBOV); SARS-CoV-2; cytokine release syndrome.