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Type: Journal article
Title: Macrophage-derived proinflammatory factors contribute to the development of arthritis and myositis after infection with an arthrogenic alphavirus
Author: Lidbury, B.
Rulli, N.
Suhrbier, A.
Smith, P.
McColl, S.
Cunningham, A.
Tarkowski, A.
van Rooijen, N.
Fraser, R.
Mahalingham, S.
Citation: Journal of Infectious Diseases, 2008; 197(11):1585-1593
Publisher: Univ Chicago Press
Issue Date: 2008
ISSN: 0022-1899
Statement of
Brett A. Lidbury, Nestor E. Rulli, Andreas Suhrbier, Paul N. Smith, Shaun R. McColl, Anthony L. Cunningham, Andrej Tarkowski, Nico van Rooijen, Robert J. Fraser and Suresh Mahalingam
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 mimics RRV disease 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–α, interferon–γ, 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 κB 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.
Keywords: Ankle; Muscles; Synovial Fluid; Macrophages; Animals; Humans; Mice; Ross River virus; Alphavirus Infections; Arthritis; Myositis; Body Weight; Cytokines; Leukocyte Reduction Procedures; Severity of Illness Index; Adult; Middle Aged
RMID: 0020080685
DOI: 10.1086/587841
Appears in Collections:Molecular and Biomedical Science publications

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