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

Juliane Lokau; Florian Kleinegger; Yvonne Garbers; Georg H Waetzig; Joachim Grötzinger; Stefan Rose-John; Johannes Haybaeck; Christoph Garbers

doi:10.1371/journal.pone.0232612

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

PLoS One. 2020 May 4;15(5):e0232612. doi: 10.1371/journal.pone.0232612. eCollection 2020.

Authors

Juliane Lokau¹, Florian Kleinegger², Yvonne Garbers³, Georg H Waetzig⁴, Joachim Grötzinger⁵, Stefan Rose-John⁵, Johannes Haybaeck^{1

2

6}, Christoph Garbers¹

Affiliations

¹ Department of Pathology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
² Diagnostic & Research Center for Molecular BioMedicine, Institute of Pathology, Medical University of Graz, Graz, Austria.
³ Institute of Psychology, Kiel University, Kiel, Germany.
⁴ CONARIS Research Institute AG, Kiel, Germany.
⁵ Institute of Biochemistry, Kiel University, Kiel, Germany.
⁶ Department of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck, Innsbruck, Austria.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal, Humanized / pharmacology*
Cell Proliferation / drug effects
Cell Survival
Cytokines / pharmacology
Hep G2 Cells
Humans
Interleukin-6 / metabolism*
Mice
RAW 264.7 Cells
Rats
Receptors, Interleukin-6 / metabolism*
Signal Transduction / drug effects
U937 Cells

Substances

Antibodies, Monoclonal, Humanized
Cytokines
IL6R protein, human
Il6ra protein, mouse
Interleukin-6
Receptors, Interleukin-6
tocilizumab

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (DFG; project 125440785 – SFB 877 A10 and A14 to CG; http://www.dfg.de). CONARIS Research AG provided support in the form of salaries for author G.H.W. The specific role of this author is articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.