Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.

Part of the Togaviridae family, alphaviruses, including chikungunya virus (CHIKV), Sindbis virus (SINV) and Ross River virus (RRV), are able to cause significant inflammatory pathologies ranging from arthritis to encephalitis. Following symptomatic infection with arthritis-associated alphaviruses, p...

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Autores principales: Adam Taylor, Kuo-Ching Sheng, Lara J Herrero, Weiqiang Chen, Nestor E Rulli, Suresh Mahalingam
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:7386531b31a34745a7c5e75c3fb9801b2021-11-18T09:00:12ZMethotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.1932-620310.1371/journal.pone.0071146https://doaj.org/article/7386531b31a34745a7c5e75c3fb9801b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23951095/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Part of the Togaviridae family, alphaviruses, including chikungunya virus (CHIKV), Sindbis virus (SINV) and 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 and 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 understand its therapeutic potential for alphaviral-induced musculoskeletal disease and 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 and 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 and chemokines, the viral load increased at early time points post infection in the serum and quadriceps of MTX treated mice, possibly contributing to disease pathogenesis. Results suggest that MTX treatment of acute RRVD in mice provides no therapeutic benefit and underline the importance of inflammatory monocytes in alphaviral induced arthritides.Adam TaylorKuo-Ching ShengLara J HerreroWeiqiang ChenNestor E RulliSuresh MahalingamPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e71146 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Adam Taylor
Kuo-Ching Sheng
Lara J Herrero
Weiqiang Chen
Nestor E Rulli
Suresh Mahalingam
Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.
description Part of the Togaviridae family, alphaviruses, including chikungunya virus (CHIKV), Sindbis virus (SINV) and 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 and 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 understand its therapeutic potential for alphaviral-induced musculoskeletal disease and 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 and 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 and chemokines, the viral load increased at early time points post infection in the serum and quadriceps of MTX treated mice, possibly contributing to disease pathogenesis. Results suggest that MTX treatment of acute RRVD in mice provides no therapeutic benefit and underline the importance of inflammatory monocytes in alphaviral induced arthritides.
format article
author Adam Taylor
Kuo-Ching Sheng
Lara J Herrero
Weiqiang Chen
Nestor E Rulli
Suresh Mahalingam
author_facet Adam Taylor
Kuo-Ching Sheng
Lara J Herrero
Weiqiang Chen
Nestor E Rulli
Suresh Mahalingam
author_sort Adam Taylor
title Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.
title_short Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.
title_full Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.
title_fullStr Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.
title_full_unstemmed Methotrexate treatment causes early onset of disease in a mouse model of Ross River virus-induced inflammatory disease through increased monocyte production.
title_sort methotrexate treatment causes early onset of disease in a mouse model of ross river virus-induced inflammatory disease through increased monocyte production.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/7386531b31a34745a7c5e75c3fb9801b
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AT kuochingsheng methotrexatetreatmentcausesearlyonsetofdiseaseinamousemodelofrossrivervirusinducedinflammatorydiseasethroughincreasedmonocyteproduction
AT larajherrero methotrexatetreatmentcausesearlyonsetofdiseaseinamousemodelofrossrivervirusinducedinflammatorydiseasethroughincreasedmonocyteproduction
AT weiqiangchen methotrexatetreatmentcausesearlyonsetofdiseaseinamousemodelofrossrivervirusinducedinflammatorydiseasethroughincreasedmonocyteproduction
AT nestorerulli methotrexatetreatmentcausesearlyonsetofdiseaseinamousemodelofrossrivervirusinducedinflammatorydiseasethroughincreasedmonocyteproduction
AT sureshmahalingam methotrexatetreatmentcausesearlyonsetofdiseaseinamousemodelofrossrivervirusinducedinflammatorydiseasethroughincreasedmonocyteproduction
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