title: 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.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Sommer
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Erika
authors.initials: E
authors.lastname: Engelowski
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Baran
authors.affiliation: Institute of Biochemistry, Medical Faculty, Christian-Albrechts-University, D-24098 Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Garbers
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Doreen M
authors.initials: DM
authors.lastname: Floss
authors.affiliation: Institute of Biochemistry and Molecular Biology II, Medical Faculty, Heinrich-Heine-University, D-40225 Düsseldorf, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Scheller
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D003092:Colitis / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D016264:Dextran Sulfate; D003911:Dextrans / Q000378:metabolism; D004198:Disease Susceptibility; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000187:drug effects; D019947:Receptors, Interleukin-6 / Q000172:deficiency / Q000378:metabolism*; D015431:Weight Loss
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D003911:Dextrans; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; C015219:fluorescein isothiocyanate dextran; C577686:interleukin-6, mouse; D016264:Dextran Sulfate; C045073:Cre recombinase; D019426:Integrases; D016650:Fluorescein-5-isothiocyanate