title: Interleukin-6: Biology, signaling and strategies of blockade.
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.
authors.affiliation: Institute of Biology, Otto-von-Guericke-University, Universitätsplatz 2, 39106 Magdeburg, Germany. Electronic address: fred.schaper@ovgu.de.
authors.forename: Fred
authors.initials: F
authors.lastname: Schaper
authors.affiliation: Institute of Biochemistry, Christian-Albrechts-University, Olshausenstrasse 40, 24098 Kiel, Germany. Electronic address: rose-john@biochem.uni-kiel.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D015850:Interleukin-6 / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D050791:STAT Transcription Factors / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D050791:STAT Transcription Factors
keywords: Cytokine; Inflammation; Receptor; Signal transduction; Trans-signaling