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.
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.
Authors: Nicholas J C King; Suresh Mahalingam; Ali Zaid; Kothila Tharmarajah; Helen Mostafavi; Joseph R Freitas; Kuo-Ching Sheng; Suan-Sin Foo; Weiqiang Chen; Jelena Vider; Xiang Liu; Nicholas P West; Lara J Herrero; Adam Taylor; Laura K Mackay; Daniel R Getts Journal: mBio Date: 2020-03-03 Impact factor: 7.867
Authors: Cooper K Hayes; Douglas R Wilcox; Yuchen Yang; Grace K Coleman; Melissa A Brown; Richard Longnecker Journal: PLoS Pathog Date: 2021-02-01 Impact factor: 6.823
Authors: Isaclaudia Gomes de Azevedo-Quintanilha; Mariana Macedo Campos; Ana Paula Teixeira Monteiro; Alessandra Dantas do Nascimento; Andrea Surrage Calheiros; Douglas Mathias Oliveira; Suelen Silva Gomes Dias; Vinicius Cardoso Soares; Julia da Cunha Santos; Isabel Tavares; Thiago Moreno Lopes Souza; Eugenio D Hottz; Fernando A Bozza; Patricia T Bozza Journal: Front Immunol Date: 2022-09-15 Impact factor: 8.786