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

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 cytok...

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Bibliographic Details
Published in:PloS one 2020-05, Vol.15 (5), p.e0232612-e0232612
Main Authors: Lokau, Juliane, Kleinegger, Florian, Garbers, Yvonne, Waetzig, Georg H, Grötzinger, Joachim, Rose-John, Stefan, Haybaeck, Johannes, Garbers, Christoph
Format: Article
Language:English
Subjects:
Amino acids
Antiarthritic agents
Antibodies
Arthritis
Biochemistry
Biological effects
Biology and Life Sciences
Cell lines
Cytokines
Disease
Diseases
Immunoglobulins
Immunologic factors
Immunosuppressive agents
Inflammatory diseases
Interleukin 6
Interleukins
Medical research
Medical treatment
Medicine and Health Sciences
Monoclonal antibodies
Pathology
Physical Sciences
Research and Analysis Methods
Rheumatoid arthritis
Rheumatoid factor
Signaling
Tocilizumab
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0232612