Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production
Autor(es): Taylor Adam, Sheng Kuo-Ching, Herrero Lara J, Chen Weiqiang, Rulli Nestor E, Mahalingam Suresh
Resumo: Part of the Togaviridae family, alphaviruses, including chikungunya virus (CHIKV), Sindbis virus (SINV) - Ross River virus (RRV), are able to cause significant inflammatory pathologies ranging from arthritis to encephalitis. Following symptomatic infection with arthritis-associated alphaviruses, patients often experience severe joint pain, affecting distal - small joints, which can last six months or longer. Recently, methotrexate (MTX), a disease modifying anti-rheumatic drug (DMARD), was used to treat patients experiencing chronic rheumatic symptoms following infection with CHIKV. Here, the effect of MTX on Ross River virus disease (RRVD) in mice was examined to better underst- its therapeutic potential for alphaviral-induced musculoskeletal disease - to further our knowledge of the development of alphaviral pathologies. Using a mouse model, we analyzed the effect of MTX on RRVD. RRV disease pathogenesis in response to MTX treatment was determined by measuring levels of proinflammatory factors, cellular infiltrates, viral titer - histological analysis of infected tissues. RRV-infected mice receiving MTX treatment rapidly developed musculoskeletal disease, which correlated with a significant influx of inflammatory cell infiltrates into the skeletal muscle tissue. Although no difference was observed in the level of proinflammatory cytokines - chemokines, the viral load increased at early time points post infection in the serum - quadriceps of MTX treated mice, possibly contributing to disease pathogenesis. Results suggest that MTX treatment of acute RRVD in mice provides no therapeutic benefit - underline the importance of inflammatory monocytes in alphaviral induced arthritides.
Imprenta: PloS One, v. 8, n. 8, p. e71146, 2013
Identificador do objeto digital: 10.1371/journal.pone.0071146
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Immunology
Data de publicação: 2013
