Collagen-induced arthritis is exacerbated in IL-10-deficient mice

Arthritis Res Ther. 2003;5(1):R18-24. doi: 10.1186/ar601. Epub 2002 Oct 21.


IL-10 is a potent immunoregulatory cytokine attenuating a wide range of immune effector and inflammatory responses. In the present study, we assess whether endogenous levels of IL-10 function to regulate the incidence and severity of collagen-induced arthritis. DBA/1 wildtype (WT), heterozygous (IL-10+/-) and homozygous (IL-10-/-) IL-10-deficient mice were immunized with type II collagen. Development of arthritis was monitored over time, and collagen-specific cytokine production and anticollagen antibodies were assessed. Arthritis developed progressively in mice immunized with collagen, and 100% of the WT, IL-10+/-, and IL-10-/- mice were arthritic at 35 days. However, the severity of arthritis in the IL-10-/- mice was significantly greater than that in WT or IL-1+/- animals. Disease severity was associated with reduced IFN-gamma levels and a dramatic increase in CD11b-positive macrophages. Paradoxically, both the IgG1 and IgG2a anticollagen antibody responses were also significantly reduced. These data demonstrate that IL-10 is capable of controlling disease severity through a mechanism that involves IFN-gamma. Since IL-10 levels are elevated in rheumatoid arthritis synovial fluid, these findings may have relevance to rheumatoid arthritis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • Arthritis / chemically induced
  • Arthritis / immunology*
  • Arthritis / pathology
  • CD11b Antigen / analysis
  • Cell Division
  • Cells, Cultured
  • Collagen / immunology
  • Disease Progression
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-10 / physiology*
  • Mice
  • Mice, Inbred DBA
  • Mice, Knockout
  • Spleen / cytology


  • CD11b Antigen
  • Interleukin-10
  • Interferon-gamma
  • Collagen