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Lokau, J; Kleinegger, F; Garbers, Y; Waetzig, GH; Grötzinger, J; Rose-John, S; Haybaeck, J; Garbers, C.
Tocilizumab does not block interleukin-6 (IL-6) signaling in murine cells.
PLoS One. 2020; 15(5): e0232612-e0232612.
Doi: 10.1371/journal.pone.0232612
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- Co-authors Med Uni Graz
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Haybäck Johannes
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Kleinegger Florian
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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.