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Cytokine Growth Factor Rev. 2015 Oct;26(5):475-87. doi: 10.1016/j.cytogfr.2015.07.004. Epub 2015 Jul 4.

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

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Institute of Biology, Otto-von-Guericke-University, Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address:
Institute of Biochemistry, Christian-Albrechts-University, Olshausenstrasse 40, 24098 Kiel, Germany. Electronic address:


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.


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

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