Therapeutic blockade of the interleukin-6 receptor (IL-6R) allows sIL-6R generation by proteolytic cleavage

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Niklas Prenissl1, Juliane Lokau2, Stefan Rose-John1

  • 1Institute of Biochemistry, Kiel University, 24118 Kiel, Germany.

Cytokine
|December 18, 2018
PubMed

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.

Keywords:
Interleukin-6Interleukin-6 receptorProteolysisTocilizumabTrans-signaling

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