Interleukin-6, but not the interleukin-6 receptor plays a role in recovery from dextran sodium sulfate-induced colitis.

Abstract

Interleukin (IL)-6-deficient, but not IL-6 receptor (IL-6R)‑deficient mice present with a delayed skin wound healing phenotype. Since IL-6 solely signals via the IL-6R and glycoprotein 130 (gp130), Il-6r-deficient mice are expected to exhibit a similar phenotype as Il-6-deficient mice. However, p28 (IL-30) and ciliary neurotrophic factor (CNTF) have been identified as additional low‑affinity ligands of the IL-6R/gp130/LIFR complex. IL-6 plays an inflammatory and regenerative role in inflammatory bowel disease (IBD). In the present study, we compared Il-6r-deficient mice with mice treated with neutralizing IL-6 monoclonal antibody (mAb) in a model of dextran sodium sulfate (DSS)-induced colitis. Our results, in agreement with those of previous reports, demonstrated that IL-6 mAbs slightly attenuated DSS-induced colitis during the regeneration phase. Il-6r-deficient mice and mice with tissue-specific deletion of the Il-6r in the myeloid cell lineage (LysMCre) with acute and chronic DSS-induced colitis were, however, indistinguishable from wild-type mice. Our data suggest that IL-6 and IL-6R have an additional role in colitis, apart from the IL-6/IL-6R classic and trans-signaling.

• Authors: Jan Sommer, Erika Engelowski, Paul Baran, Christoph Garbers, Doreen M Floss, Jürgen Scheller
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 34 Issue 3 Pg. 651-60 (Sep 2014) ISSN: 1791-244X [Electronic] Greece
• PMID: 24993179 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Dextrans
• Interleukin-6
• Receptors, Interleukin-6
• fluorescein isothiocyanate dextran
• interleukin-6, mouse
• Dextran Sulfate
• Cre recombinase
• Integrases
• Fluorescein-5-isothiocyanate

Topics

• Animals
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Neutralizing (pharmacology)
• Colitis (blood, chemically induced, metabolism)
• Colon (drug effects, pathology)
• Dextran Sulfate
• Dextrans (metabolism)
• Disease Susceptibility
• Fluorescein-5-isothiocyanate (analogs & derivatives, metabolism)
• Integrases (metabolism)
• Interleukin-6 (metabolism)
• Male
• Mice, Inbred C57BL
• Organ Specificity (drug effects)
• Receptors, Interleukin-6 (deficiency, metabolism)
• Weight Loss