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  • Inhibition of Interleukin-1β Signaling by Anakinra Demonstrates a Critical Role of Bone Loss in Experimental Arthritogenic Alphavirus Infections

    Author(s)
    Wolf, Stefan
    Taylor, Adam
    Zaid, Ali
    Freitas, Joseph
    Herrero, Lara J
    Rao, Shambhavi
    Suhrbier, Andreas
    Forwood, Mark R
    Bucala, Richard
    Mahalingam, Suresh
    Griffith University Author(s)
    Forwood, Mark R.
    Taylor, Adam
    Zaid, Ali
    Herrero, Lara J.
    Mahalingam, Suresh
    Year published
    2019
    Metadata
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    Abstract
    Objective: Arthritogenic alphaviruses, such as Ross River virus (RRV) and chikungunya virus (CHIKV), particularly affect joints of the extremities and can lead to debilitating and potentially chronic polyarthritis/polyarthralgia. The innate immune response of the host plays a crucial role in inducing proinflammatory host factors, leading to tissue destruction and bone loss in the joints. This study was performed to assess how the inhibition of interleukin-1β (IL-1β) signaling using the clinical rheumatoid arthritis drug anakinra influences bone loss in mice with arthritogenic alphavirus infections. Methods: Mice (n = 5 per ...
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    Objective: Arthritogenic alphaviruses, such as Ross River virus (RRV) and chikungunya virus (CHIKV), particularly affect joints of the extremities and can lead to debilitating and potentially chronic polyarthritis/polyarthralgia. The innate immune response of the host plays a crucial role in inducing proinflammatory host factors, leading to tissue destruction and bone loss in the joints. This study was performed to assess how the inhibition of interleukin-1β (IL-1β) signaling using the clinical rheumatoid arthritis drug anakinra influences bone loss in mice with arthritogenic alphavirus infections. Methods: Mice (n = 5 per group) were infected with RRV or CHIKV and then treated with anakinra. Weight gain and disease severity were measured, tissue viral titers were determined, and histologic changes in joint tissues were assessed. Results: Anakinra therapy reduced RRV- and CHIKV-induced bone loss in this murine model (P < 0.001 and P < 0.05, respectively). Histologic analysis of the knee joint showed that treatment with anakinra decreased epiphyseal growth plate thinning, loss of epiphyseal bone volume, and osteoclastogenesis in the tibia. Importantly, pharmacologic IL-1 receptor (IL-1R) blockade did not improve other clinical features, including disease score, weight loss, or viremia. Conclusion: The present findings suggest that anakinra therapy may reduce bone loss in experimental murine models of RRV and CHIKV. Further investigations are needed to assess the potential therapeutic benefits of anakinra in patients with arthritogenic alphavirus disease.
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    Journal Title
    Arthritis and Rheumatology
    DOI
    https://doi.org/10.1002/art.40856
    Note
    This publication has been entered into Griffith Research Online as an Advanced Online Version.
    Subject
    Clinical sciences
    Publication URI
    http://hdl.handle.net/10072/386081
    Collection
    • Journal articles

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