Abnormal T cell activation caused by the imbalance of the IL-1/IL-1R antagonist system is responsible for the development of experimental autoimmune encephalomyelitis

Int Immunol. 2006 Feb;18(2):399-407. doi: 10.1093/intimm/dxh379. Epub 2006 Jan 13.


IL-1 is a pro-inflammatory cytokine that plays an important role in inflammation and host responses to infection. We have previously shown that imbalances in the IL-1 and IL-1R antagonist (IL-1Ra) system cause the development of inflammatory diseases. To explore the role of the IL-1/IL-1Ra system in autoimmune disease, we analyzed myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) in mice bearing targeted disruptions of the IL-1alpha, IL-1beta, IL-1alpha and IL-1beta (IL-1) or IL-1Ra genes. IL-1alpha/beta double-deficient (IL-1-/-) mice exhibited significant resistance to EAE induction with a significant reduction in disease severity, while IL-1alpha-/- or IL-1beta-/- mice developed EAE in a manner similar to wild-type mice. IL-1Ra-/- mice also developed MOG-induced EAE normally with pertussis toxin (PTx) administration. In contrast to wild-type mice, however, these mice were highly susceptible to EAE induction in the absence of PTx administration. We found that both IFN-gamma and IL-17 production and proliferation were reduced in IL-1-/- T cells upon stimulation with MOG, while IFN-gamma, IL-17 and tumor necrosis factor-alpha production and proliferation were enhanced in IL-1Ra-/- T cells. These observations suggest that the IL-1/IL-1Ra system is crucial for auto-antigen-specific T cell induction and contributes to the development of EAE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Epitopes
  • Female
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / physiology*
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Myelin Proteins
  • Myelin-Associated Glycoprotein / immunology
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptors, Interleukin-1 / immunology
  • Sialoglycoproteins / physiology*
  • T-Lymphocytes / immunology*


  • Epitopes
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Mog protein, mouse
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Receptors, Interleukin-1
  • Sialoglycoproteins