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

Int J Mol Med. 2014 Sep;34(3):651-60. doi: 10.3892/ijmm.2014.1825. Epub 2014 Jun 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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