Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice

<p>Abstract</p> <p>Background</p> <p>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 immunos...

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Main Authors: De Clercq Erik, Aerts Joeri L, Matthys Patrick, Verbeken Erik, Padalko Elizaveta, Neyts Johan
Format: Article
Language:English
Published: BMC 2003-12-01
Series:BMC Microbiology
Subjects:
Online Access:http://www.biomedcentral.com/1471-2180/3/25
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author De Clercq Erik
Aerts Joeri L
Matthys Patrick
Verbeken Erik
Padalko Elizaveta
Neyts Johan
author_facet De Clercq Erik
Aerts Joeri L
Matthys Patrick
Verbeken Erik
Padalko Elizaveta
Neyts Johan
author_sort De Clercq Erik
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>The immunosuppressive agent MMF results in an important reduction of CBV3-induced myocarditis in a murine model.</p>
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spelling doaj.art-8dc969ab9cdf4f3d8ee1cb2ce66575392022-12-22T00:25:50ZengBMCBMC Microbiology1471-21802003-12-01312510.1186/1471-2180-3-25Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in miceDe Clercq ErikAerts Joeri LMatthys PatrickVerbeken ErikPadalko ElizavetaNeyts Johan<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>The immunosuppressive agent MMF results in an important reduction of CBV3-induced myocarditis in a murine model.</p>http://www.biomedcentral.com/1471-2180/3/25enterovirusmyocarditisantiviralcoxsackie
spellingShingle De Clercq Erik
Aerts Joeri L
Matthys Patrick
Verbeken Erik
Padalko Elizaveta
Neyts Johan
Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice
BMC Microbiology
enterovirus
myocarditis
antiviral
coxsackie
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 enterovirus
myocarditis
antiviral
coxsackie
url http://www.biomedcentral.com/1471-2180/3/25
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