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Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice
BACKGROUND: Viral replication as well as an immunopathological component are assumed to be involved in the development of coxsackie B virus (CBV)-induced myocarditis. We observed that mycophenolic acid (MPA), the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF), inhibits...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC317291/ https://www.ncbi.nlm.nih.gov/pubmed/14687413 http://dx.doi.org/10.1186/1471-2180-3-25 |
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author | Padalko, Elizaveta Verbeken, Erik Matthys, Patrick Aerts, Joeri L De Clercq, Erik Neyts, Johan |
author_facet | Padalko, Elizaveta Verbeken, Erik Matthys, Patrick Aerts, Joeri L De Clercq, Erik Neyts, Johan |
author_sort | Padalko, Elizaveta |
collection | PubMed |
description | BACKGROUND: Viral replication as well as an immunopathological component are assumed to be involved in the development of coxsackie B virus (CBV)-induced myocarditis. We observed that mycophenolic acid (MPA), the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF), inhibits coxsackie B3 virus (CBV3) replication in primary Human myocardial fibroblasts. We therefore studied whether MMF, which is thus endowed with a direct antiviral as well as immunosuppressive effect, may prevent CBV-induced myocarditis in a murine model. RESULTS: Four week old C3H-mice were infected with CBV3 and received twice daily, for 7 consecutive days (from one day before to 5 days post-virus inoculation) treatment with MMF via oral gavage. Treatment with MMF resulted in a significant reduction in the development of CBV-induced myocarditis as assessed by morphometric analysis, i.e. 78% reduction when MMF was administered at 300 mg/kg/day (p < 0.001), 65% reduction at 200 mg/kg/day (p < 0.001), and 52% reduction at 100 mg/kg/day (p = 0.001). The beneficial effect could not be ascribed to inhibition of viral replication since titers of infectious virus and viral RNA in heart tissue were increased in MMF-treated animals as compared to untreated animals. CONCLUSION: The immunosuppressive agent MMF results in an important reduction of CBV3-induced myocarditis in a murine model. |
format | Text |
id | pubmed-317291 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-3172912004-01-23 Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice Padalko, Elizaveta Verbeken, Erik Matthys, Patrick Aerts, Joeri L De Clercq, Erik Neyts, Johan BMC Microbiol Research Article BACKGROUND: Viral replication as well as an immunopathological component are assumed to be involved in the development of coxsackie B virus (CBV)-induced myocarditis. We observed that mycophenolic acid (MPA), the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF), inhibits coxsackie B3 virus (CBV3) replication in primary Human myocardial fibroblasts. We therefore studied whether MMF, which is thus endowed with a direct antiviral as well as immunosuppressive effect, may prevent CBV-induced myocarditis in a murine model. RESULTS: Four week old C3H-mice were infected with CBV3 and received twice daily, for 7 consecutive days (from one day before to 5 days post-virus inoculation) treatment with MMF via oral gavage. Treatment with MMF resulted in a significant reduction in the development of CBV-induced myocarditis as assessed by morphometric analysis, i.e. 78% reduction when MMF was administered at 300 mg/kg/day (p < 0.001), 65% reduction at 200 mg/kg/day (p < 0.001), and 52% reduction at 100 mg/kg/day (p = 0.001). The beneficial effect could not be ascribed to inhibition of viral replication since titers of infectious virus and viral RNA in heart tissue were increased in MMF-treated animals as compared to untreated animals. CONCLUSION: The immunosuppressive agent MMF results in an important reduction of CBV3-induced myocarditis in a murine model. BioMed Central 2003-12-21 /pmc/articles/PMC317291/ /pubmed/14687413 http://dx.doi.org/10.1186/1471-2180-3-25 Text en Copyright © 2003 Padalko et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. |
spellingShingle | Research Article Padalko, Elizaveta Verbeken, Erik Matthys, Patrick Aerts, Joeri L De Clercq, Erik Neyts, Johan Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice |
title | Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice |
title_full | Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice |
title_fullStr | Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice |
title_full_unstemmed | Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice |
title_short | Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice |
title_sort | mycophenolate mofetil inhibits the development of coxsackie b3-virus-induced myocarditis in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC317291/ https://www.ncbi.nlm.nih.gov/pubmed/14687413 http://dx.doi.org/10.1186/1471-2180-3-25 |
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