IL-6 blockade attenuates the development of murine sclerodermatous chronic graft-versus-host disease

J Invest Dermatol. 2012 Dec;132(12):2752-61. doi: 10.1038/jid.2012.226. Epub 2012 Jul 19.


Systemic sclerosis (scleroderma) is a connective tissue disease characterized by excessive extracellular matrix deposition in the skin and visceral organs. Serum IL-6 levels are reported to be elevated in human scleroderma and chronic graft-versus-host disease (cGVHD) patients. IL-6 blockade using anti-IL-6 receptor mAb (anti-IL-6R mAb) results in amelioration of the pathologic symptoms of some autoimmune diseases such as rheumatoid arthritis and juvenile idiopathic arthritis. In this study, we examined the effects of anti-IL-6R mAb on either prevention or treatment of murine sclerodermatous cGVHD (Scl-cGVHD). We found that serum IL-6 levels in Scl-cGVHD mice gradually increased after bone marrow transplantation. Administration of anti-IL-6R mAb attenuated the development of severe Scl-cGVHD and fibrosis and resulted in an increase in CD4(+)CD25(+)FoxP3(+) regulatory T cells. However, treatment of established Scl-cGVHD with anti-IL-6R mAb showed no effects on disease severity. The effects of anti-IL-6R mAb were mostly inhibited by anti-CD25 mAb. Together, our results indicate that IL-6 has an important role in the pathogenesis of Scl-cGVHD. IL-6 blockade may be an effective approach for preventing Scl-cGVHD and treating cGVHD and scleroderma in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibody Specificity / immunology
  • Bone Marrow Transplantation / adverse effects*
  • Bone Marrow Transplantation / immunology
  • Chronic Disease
  • Disease Models, Animal
  • Female
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / immunology
  • Graft vs Host Disease* / prevention & control
  • Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Receptors, Interleukin-6 / immunology
  • Scleroderma, Systemic* / complications
  • Scleroderma, Systemic* / drug therapy
  • Scleroderma, Systemic* / immunology
  • Severity of Illness Index
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology


  • Antibodies, Monoclonal
  • Il2ra protein, mouse
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-6
  • Receptors, Interleukin-6