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Oncogenesis. 2016 Nov 21;5(11):e270. doi: 10.1038/oncsis.2016.71.

Classic IL-6R signalling is dispensable for intestinal epithelial proliferation and repair.

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Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
First Medical Department, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
CONARIS Research Institute AG, Kiel, Germany.
Ferring Pharmaceuticals A/S, Copenhagen, Denmark.
Institute of Biochemistry, Kiel University, Kiel, Germany.


Inflammatory bowel disease is characterized by disturbed cytokine signalling in the mucosa. Inhibition of the proinflammatory interleukin (IL)-6 pathway is a promising new therapeutic strategy, but safety concerns arise as IL-6 signalling also contributes to epithelial repair of the intestinal mucosa. To which extent IL-6 classic or trans-signalling contributes to intestinal repair remains elusive. We tested the influence of IL-6 classic signalling on intestinal repair and proliferation. Whereas IL-6 induced STAT3 phosphorylation in the colonic cancer cell lines, primary non-malignant intestinal organoids did not respond to IL-6 classic signalling. Mice deficient in intestinal IL-6R (IL-6RΔIEC mice) did not display increased susceptibility to acute dextran sulfate sodium (DSS)-induced colitis. In the azoxymethane DSS model IL-6RΔIEC mice were not protected from inflammation-induced carcinogenesis but showed comparable tumor load to wild-type mice. These data indicate that classic signalling is not the major pathway to transduce IL-6 stimuli into the intestinal epithelium.

Conflict of interest statement

GHW is employed by CONARIS Research Institute AG (a company commercially developing sgp130Fc proteins); SS and SR-J are shareholders of CONARIS, and both are inventors of patents owned by CONARIS. The other authors declare no conflict of interest.

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