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

AbstractOBJECTIVESThis study examines the efficacy of FTY720 (FTY), a new immunosuppressor, in the treatment of acute viral myocarditis in a murine model.BACKGROUNDImmunosuppressive agents have no proven therapeutic efficacy in experimental or clinical myocarditis.METHODSEncephalomyocarditis 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.RESULTSIn 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.CONCLUSIONSFTY720 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