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

Elizaveta Padalko¹ , Erik Verbeken² , Patrick Matthys³ , Joeri L Aerts⁴ , Erik De Clercq¹ and Johan Neyts¹

¹Laboratory of Chemotherapy, Rega Institute, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium

²Division of Morphology and Molecular Pathology, University Hospitals, Minderbroedersstraat 12, B-3000 Leuven, Belgium

³Laboratory of Immunobiology, Rega Institute, Katholieke Universiteit, Minderbroedersstraat 10, B-3000 Leuven, Belgium

⁴Experimental Laboratory Medicine, University Hospitals, Herestaat 49, B-3000 Leuven, Belgium

author email corresponding author email

BMC Microbiology 2003, 3:25doi:10.1186/1471-2180-3-25


Published:	21 December 2003

Abstract

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.