Dependence on interferon‐γ for the spontaneous occurrence of arthritis in DBA/1 mice

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Abstract
Objective Male DBA/1 mice are known to spontaneously develop arthritis in the hind legs. The present study was undertaken to investigate the role of endogenous interferon-γ (IFNγ) in the pathogenesis of this ankylosing enthesopathy. Methods The role of IFNγ was studied by examining the development of arthritis in IFNγ receptor–knockout (IFNγR-KO) DBA/1 mice as compared with wild-type mice, and by treatment of wild-type mice with monoclonal anti-IFNγ antibody. IFNγ-disrupted and wild-type mice were mixed and housed in the same cage, and clinical symptoms of arthritis were assessed weekly for at least 9 weeks. Histologic examination was performed at the end of the experiment. Results In DBA/1 wild-type mice, 70% of the animals developed clinical symptoms of spontaneous arthritis, such as redness and swelling of the proximal interphalangeal joints, toe stiffness, and ankylosis. As evident from microscopic evaluation, the arthritis was mainly characterized by formation of new cartilage and bone, originating at the entheses and leading to ankylosis. The incidence and severity of arthritis, both clinically and histologically, were significantly reduced in IFNγR-KO mice. In wild-type mice, neutralizing anti-IFNγ antibody inhibited the occurrence of the disease for the duration of treatment. Conclusion The results suggest that endogenous IFNγ plays an important role in the initial stages of spontaneous arthritis, and that the inflammatory components in its pathogenesis are more prominent than has been believed. In view of the similarity between this disease and spondylarthropathies in humans, the data suggest that endogenous IFNγ may also play a disease-promoting role in the human condition and thus may serve as a target for therapy.
Funding Information
  • Fund for Scientific Research Flanders, the regional government of Flanders
  • Belgian federal government (Interuniversity Network for Fundamental Research)