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  • Macrophage-Derived Proinflammatory Factors Contribute to the Development of Arthritis and Myositis after Infection with an Arthrogenic Alpohavirus

    Author(s)
    Lidbury, Brett A.
    Rulli, Nestor E.
    Suhrbier, Andreas
    Smith, Paul N;
    McColl, Shaun R.
    Cunningham, Anthony L.
    Tarkowski, Andrej
    van Rooijen, Nico
    Fraser, Robert J.
    Mahalingam, Suresh
    Griffith University Author(s)
    Mahalingam, Suresh
    Rulli, Nestor
    Year published
    2008
    Metadata
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    Abstract
    Alphaviruses, such as chikungunya virus and Ross River virus (RRV), are associated with outbreaks of infectious rheumatic disease in humans worldwide. Using an established mouse model of disease that mimicsRRVdisease in humans, we showed that macrophage-derived factors are critical in the development of striated muscle and joint tissue damage. Histologic analyses of muscle and ankle joint tissues demonstrated a substantial reduction in inflammatory infiltrates in infected mice depleted of macrophages (i.e., "macrophage-depleted mice"). Levels of the proinflammatory factors tumor necrosis factor-a, interferon-?, and macrophage ...
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    Alphaviruses, such as chikungunya virus and Ross River virus (RRV), are associated with outbreaks of infectious rheumatic disease in humans worldwide. Using an established mouse model of disease that mimicsRRVdisease in humans, we showed that macrophage-derived factors are critical in the development of striated muscle and joint tissue damage. Histologic analyses of muscle and ankle joint tissues demonstrated a substantial reduction in inflammatory infiltrates in infected mice depleted of macrophages (i.e., "macrophage-depleted mice"). Levels of the proinflammatory factors tumor necrosis factor-a, interferon-?, and macrophage chemoattractant protein-1 were also dramatically reduced in tissue samples obtained from infected macrophage-depleted mice, compared with samples obtained from infected mice without macrophage depletion. These factors were also detected in the synovial fluid of patients with RRV-induced polyarthritis. Neutralization of these factors reduced the severity of disease in mice, whereas blocking nuclear factor ?B by treatment with sulfasalazine ameliorated RRV inflammatory disease and tissue damage. To our knowledge, these findings are the first to demonstrate that macrophage-derived products play important roles in the development of arthritis and myositis triggered by alphavirus infection.
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    Journal Title
    Journal of Infectious Diseases
    Volume
    197
    Issue
    11
    DOI
    https://doi.org/10.1086/587841
    Subject
    Medical Virology
    Biological Sciences
    Medical and Health Sciences
    Publication URI
    http://hdl.handle.net/10072/38004
    Collection
    • Journal articles

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