Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice

Eur J Immunol. 1996 Dec;26(12):2933-8. doi: 10.1002/eji.1830261219.


Collagen-induced arthritis (CIA) is an animal model for rheumatoid arthritis. The disease is elicited by immunization of genetically susceptible DBA/1 mice with type II collagen, resulting in a debilitating arthritis characterized by inflammation and involvement of multiple joints. We investigated the role of endogenous interleukin (IL)-12 in the pathogenesis of this disease by undertaking an analysis of IL-12-deficient mice on the DBA/1 genetic background after immunization with type II collagen. Both the incidence and severity of disease were significantly reduced in mice unable to produce biologically active IL-12. Concomitant decreases were observed in serum levels of pathogenic, collagen-specific IgG2a antibodies and collagen-induced secretion of interferon-gamma by immune splenocytes in vitro, consistent with an impaired T helper-1 response. There were, however, a few animals which developed severe disease in a single paw in spite of this highly diminished Th1 response. Taken together, these results demonstrate an important role for IL-12 in the pathogenesis of CIA, although it is not absolutely required for disease development.

MeSH terms

  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / epidemiology*
  • Arthritis, Experimental / pathology*
  • Collagen / immunology
  • Collagen / toxicity*
  • Immunoglobulin G / immunology
  • Incidence
  • Interleukin-12 / deficiency*
  • Interleukin-12 / genetics
  • Interleukin-12 / toxicity*
  • Mice
  • Mice, Inbred DBA
  • Mice, Mutant Strains


  • Immunoglobulin G
  • Interleukin-12
  • Collagen