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Prenissl, N; Lokau, J; Rose-John, S; Haybaeck, J; Garbers, C.
Therapeutic blockade of the interleukin-6 receptor (IL-6R) allows sIL-6R generation by proteolytic cleavage.
Cytokine. 2019; 114(4):1-5 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Haybäck Johannes
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Abstract:
Blockade of the interleukin-6 receptor (IL-6R) is a successful therapeutic strategy in various inflammatory diseases. IL-6 can signal via membrane-bound (classic signaling) and soluble forms (sIL-6R, trans-signaling) of the IL-6R. Trans-signaling is causative for the pro-inflammatory properties of IL-6, and the selective inhibition of this pathway holds the promise to cause less side effects than the global blockade of IL-6 signaling. We have recently shown that the majority of sIL-6R in humans is generated by proteolytic cleavage of the membrane-bound IL-6R, but whether this process is influenced by therapeutic blockade of the IL-6R is unknown. In this study, we show that the monoclonal antibody tocilizumab and a single chain antibody directed against the IL-6R efficiently block IL-6 signaling, but do not prevent the proteolytic generation of sIL-6R. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Find related publications in this database (Keywords)
Interleukin-6
Interleukin-6 receptor
Trans-signaling
Proteolysis
Tocilizumab
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