Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis

Giuseppe Stabile, Antonio De Simone, Pietro Turco, Vincenzo La Rocca, Pasquale Nocerino, Costantino Astarita, Francesco Maresca, Carmine De Matteis, Tommaso Di Napoli, Eugenio Stabile, Dino Franco Vitale

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVES: This study examines the efficacy of FTY720 (FTY), a new immunosuppressor, in the treatment of acute viral myocarditis in a murine model. BACKGROUND: Immunosuppressive agents have no proven therapeutic efficacy in experimental or clinical myocarditis. METHODS: Encephalomyocarditis virus was inoculated i.p. in DBA/2 mice on day 0. Postinoculation treatment consisted of FTY 10 mg/kg/day p.o. (FTY group), or cyclosporine A (CsA) 40 mg/kg/day p.o. (CsA group) or distilled water p.o. only (control group). Survival until day 14, as well as cardiac histopathology, virus concentrations, cytokines (interleukin [IL]-2, IL-12, interferon [IFN]-gamma and tumor necrosis factor [TNF]-alpha) and nitric oxide (NO) on day 5 were examined. RESULTS: In the control and CsA groups, all mice died within 10 and 7 days, respectively. However, in the FTY group, 27% of the animals survived up to day 14. Compared with the control group, 1) histological scores were significantly lower in the FTY group but unchanged in the CsA group; 2) virus concentration was significantly higher in the CsA group but not in the FTY group; 3) expressions of IL-2, IL-12 and IFN-gamma in the heart were suppressed in both the FTY and CsA groups, though suppression was weaker in the FTY group; 4) TNF-alpha and NO were significantly increased in the CsA group but not in the FTY group. CONCLUSIONS: FTY720 had a significant therapeutic effect in acute experimental myocarditis without inducing excessive virus replication. This report is the first to describe a beneficial effect by an immunosuppressive agent in the treatment of acute viral myocarditis.

Original languageEnglish
Pages (from-to)1713-1718
Number of pages6
JournalJournal of the American College of Cardiology
Volume37
Issue number6
DOIs
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Nursing(all)

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