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      Interleukin-6: Biology, signaling and strategies of blockade.

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          Abstract

          Interleukin-6 (IL-6) is one of the most important inflammatory cytokines. IL-6 is unique in signaling via a membrane bound and a soluble receptor. Intriguingly, these two pathways strongly differ in their biologic consequences. While classic IL-6 signaling via the membrane bound receptor is mainly regenerative and protective, IL-6 trans-signaling via the soluble IL-6R is rather pro-inflammatory. Intracellular signaling of IL-6 in response to receptor activation is through STAT-dependent and STAT-independent signaling modules, which are regulated by a complex regulatory network. The complex biology of IL-6 has consequences for therapeutic targeting of this cytokine. We hypothesize that specific inhibition of the trans-signaling pathway may be superior to global blockade of IL-6 activity with help of antibodies directed against IL-6 or IL-6R.

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          Author and article information

          Journal
          Cytokine Growth Factor Rev.
          Cytokine & growth factor reviews
          1879-0305
          1359-6101
          Oct 2015
          : 26
          : 5
          Affiliations
          [1 ] Institute of Biology, Otto-von-Guericke-University, Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: fred.schaper@ovgu.de.
          [2 ] Institute of Biochemistry, Christian-Albrechts-University, Olshausenstrasse 40, 24098 Kiel, Germany. Electronic address: rose-john@biochem.uni-kiel.de.
          Article
          S1359-6101(15)00052-0
          10.1016/j.cytogfr.2015.07.004
          26189695
          bb9238fe-b613-42a1-ab4b-4b2021907711
          Copyright © 2015 Elsevier Ltd. All rights reserved.
          History

          Cytokine,Inflammation,Receptor,Signal transduction,Trans-signaling

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