Tocilizumab does not block interleukin-6 (IL-6) signaling in murine cells.

Authors:
Juliane Lokau, Florian Kleinegger, Yvonne Garbers, Georg H Waetzig, Joachim Grötzinger, Stefan Rose-John, Johannes Haybaeck, Christoph Garbers
Year of publication:
2020
Volume:
15
Issue:
5
Issn:
1932-6203
Journal title abbreviated:
PLoS ONE
Journal title long:
PloS one
Impact factor:
2.740
Abstract:
Tocilizumab is a humanized monoclonal antibody that is approved for the treatment of different human inflammatory diseases, including rheumatoid arthritis and cytokine release syndrome. Tocilizumab binds to the interleukin-6 receptor (IL-6R) and thereby blocks signaling of the pro-inflammatory cytokine IL-6. Initial studies and all authority assessment reports state that tocilizumab is effective in humans, but cannot bind to the murine or rat IL-6R and thus not block IL-6 signaling in the mouse. However, several recent studies described the use of tocilizumab in mice and reported biological effects that were attributed to IL-6 blockade. In this study, we investigate the capability of tocilizumab to block IL-6 signaling using different human and murine cell lines. Our results unequivocally confirm the original state of the art that tocilizumab blocks signaling via the human IL-6R, but does not block IL-6 signaling in murine cells.