The IL-10-/- mouse as a model of chronic Lyme arthritis. (169.16)

Abstract

IL-10 suppresses the development of arthritis in Borrelia burgdorferi infected mice. Infected IL-10-/- mice were previously found to have a robust and sustained interferon-inducible response in joint tissue, and elevated IFN-γ in sera. Treatment of IL-10-/- mice with anti-IFN-γ reduced arthritis severity and suppressed interferon-inducible transcripts to wild type levels, thereby linking dysregulation of IFN-γ to disease in the IL-10-/- mouse. Arthritis in IL-10 deficient mice was associated with elevated numbers of NK cell, NKT cell, α/β T cell, and macrophage infiltration of the infected joint. FACS lineage sorting revealed NK cells and CD4+ T cells as sources of IFN-γ in the joint tissue of IL-10-/- mice. These findings suggest the presence of a positive feedback loop in the joint tissue of infected IL-10-/- mice, where production of inflammatory chemokines, infiltration of IFN-γ producing cells, and additional production of inflammatory cytokines result in arthritis. This mechanism of arthritis is in contrast to that seen in C3H mice, where arthritis development is linked to transient production of Type I interferon, and develops independently of IFN-γ. Due to the sustained interferon response driven by NK cells and T cells, we propose the IL-10-/- mouse as a potential model to study the prolonged symptoms observed in some human Lyme disease patients.