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 hours of challenge and repeated every 72 hours. A similar effect was seen in mice treated with the same dose of α-IL-6R mAb when the treatment was delayed 48 hrs 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.
Competing Interest Statement
Reid Rubsamen, Scott Burkholz, Richard Carback, Tom Hodge, Lu Wang, and Charles Herst are employees of Flow Pharma, Inc. compensated in cash and stock, and are named inventors on various issued and pending patents assigned to Flow Pharma. Some of these patents pending are directly related to the study presented here. Paul Harris is a member of Flow Pharma's Scientific Advisory Board. Christopher Massey, and Trevor Brasel have nothing to declare.
Footnotes
Corrected affiliation. Added table of relevant references.