Macrophage-derived proinflammatory factors contribute to the development of arthritis and myositis after infection with an arthrogenic alphavirus
Autor(es): 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
Resumo: Alphaviruses, such as chikungunya virus - Ross River virus (RRV), are associated with outbreaks of infectious rheumatic disease in humans worldwide. Using an established mouse model of disease that mimics RRV disease in humans, we showed that macrophage-derived factors are critical in the development of striated muscle - joint tissue damage. Histologic analyses of muscle - 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-alpha, interferon-gamma, - 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 kappaB by treatment with sulfasalazine ameliorated RRV inflammatory disease - tissue damage. To our knowledge, these findings are the first to demonstrate that macrophage-derived products play important roles in the development of arthritis - myositis triggered by alphavirus infection."
Imprenta: The Journal of Infectious Diseases, v. 197, n. 11, p. 1585-1593, 2008
Identificador do objeto digital: 10.1086/587841
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya virus - Clinical examination ; Chikungunya Virus - Virus ; Chikungunya virus - Immunology ; Chikungunya virus - Public health
Data de publicação: 2008
