Alphaviruses, such as chikungunya virus and Ross River virus (RRV), are associated with outbreaks of infectious rheumatic disease in humans worldwide. [They are spread by insect vectors
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. [Macrophages are large white blood cells responsible for digesting pathogens and stimulating other immune cells to respond to them.]
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-alpha, interferon-gamma, 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 kappaB by treatment with sulfasalazine ameliorated RRV inflammatory disease and tissue damage. [Nuclear factor kappaB is involved in regulating cellular responses to stimuli.]
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.
Source: The Journal of Infectious Diseases. April 23, 2008. [E-pub ahead of print] PMID: 18433328 by Lidbury BA, Rulli NE, Suhrbier A, Smith PN, McColl SR, Cunningham AL, Tarkowski A, van Rooijen N, Fraser RJ, Mahalingam S. Virus and Inflammation Research Group, Faculty of Sciences, University of Canberra; Orthopedic Unit, John James Hospital, and The Australian National University Medical School, Canberra; Queensland Institute of Medical Research, Brisbane; School of Molecular and Biomedical Science, The University of Adelaide, Adelaide; Centre for Virus Research, Westmead Millennium Institute, Sydney; and Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Australia. Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden. Department of Cell Biology and Immunology Faculty of Medicine, Vrije University, Amsterdam, The Netherlands. [E-mail: