Roles of IL-1 in the development of rheumatoid arthritis: consideration from mouse models

Cytokine Growth Factor Rev. 2002 Aug-Oct;13(4-5):341-55. doi: 10.1016/s1359-6101(02)00021-7.

Abstract

Expression of inflammatory cytokines is augmented in the joints of patients with rheumatoid arthritis (RA). We found that cytokine levels are also elevated in the joints of a mouse arthritis model, human T-cell leukemia virus type I (HTLV-I) transgenic (Tg) mouse. Depletion of IL-1 by gene targeting greatly reduced the incidence of the disease, indicating the importance of this cytokine in the development of arthritis. Furthermore, IL-1 receptor antagonist (IL-1Ra)-deficient mice develop autoimmunity and arthritis spontaneously. These observations suggest that excess IL-1 signaling the causes autoimmunity. We show that IL-1 activates the immune system non-specifically by inducing CD40L and OX40 co-signaling molecules on T cells. In this review, the roles of IL-1 in the development of autoimmunity and arthritis in mouse models will be discussed.

Publication types

  • Comparative Study
  • Review

MeSH terms

  • Animals
  • Arthritis / genetics
  • Arthritis / virology
  • Arthritis, Experimental / genetics
  • Arthritis, Rheumatoid / etiology*
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / biosynthesis
  • Autoimmune Diseases / etiology*
  • Autoimmune Diseases / immunology
  • Autoimmunity / physiology
  • CD40 Antigens / physiology
  • CD40 Ligand / biosynthesis
  • CD40 Ligand / genetics
  • Crosses, Genetic
  • Cytokines / physiology
  • Disease Models, Animal
  • Gene Targeting
  • Genes, Viral
  • Human T-lymphotropic virus 1 / genetics
  • Humans
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1 / deficiency
  • Interleukin-1 / genetics
  • Interleukin-1 / physiology*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Models, Immunological
  • OX40 Ligand
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor*
  • Sialoglycoproteins / deficiency
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / physiology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
  • Tumor Necrosis Factors

Substances

  • Autoantibodies
  • CD40 Antigens
  • Cytokines
  • IL1RN protein, human
  • Il1rn protein, mouse
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1
  • Membrane Glycoproteins
  • OX40 Ligand
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • Sialoglycoproteins
  • TNFRSF4 protein, human
  • TNFSF4 protein, human
  • Tnfrsf4 protein, mouse
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factors
  • CD40 Ligand