Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma

Am J Pathol. 2012 Jan;180(1):165-76. doi: 10.1016/j.ajpath.2011.09.013. Epub 2011 Nov 7.


Activation of fibroblasts by interleukin-6 (IL-6) is implicated in the pathogenesis of scleroderma, suggesting that the inhibition of fibroblast activation may be a promising scleroderma treatment. In this study, we used an IL-6 blocking antibody (Ab) and Il-6 knockout (Il-6KO) mice to examine the role of IL-6 in the bleomycin (BLM)-induced mouse model of scleroderma. BLM was administered to C57BL/6 and Il-6KO mice to induce dermal sclerosis. BLM-treated and control phosphate-buffered saline-treated mice were treated with anti-mouse IL-6 receptor monoclonal Ab (MR16-1). Disease severity was evaluated by measuring dermal thickness and skin hardness, by counting the numbers of α-smooth muscle actin-positive cells and mast cells, and by examining the cutaneous draining lymph nodes. C57BL/6 mice with BLM induced scleroderma had elevated serum IL-6 levels and more severe dermal sclerosis than Il-6KO mice. Weekly administration of MR16-1, but not control Ab, prevented and improved dermal sclerosis, and also attenuated swelling of the draining lymph nodes. MR16-1 suppressed α-smooth muscle actin induction in IL-6-stimulated Il-6KO fibroblasts. Our results indicate that IL-6 contributes to BLM induced dermal sclerosis and that IL-6 receptor-specific monoclonal Ab may improve the symptoms of scleroderma by suppressing fibroblast activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Antibiotics, Antineoplastic / toxicity
  • Antibodies, Monoclonal / pharmacology
  • Bleomycin / toxicity
  • Cells, Cultured
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polysaccharides, Bacterial / pharmacology
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Scleroderma, Localized / chemically induced
  • Scleroderma, Localized / prevention & control*
  • Sclerosis / chemically induced
  • Skin / pathology


  • Acta2 protein, mouse
  • Actins
  • Antibiotics, Antineoplastic
  • Antibodies, Monoclonal
  • Polysaccharides, Bacterial
  • Receptors, Interleukin-6
  • Bleomycin