title: Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiovascular Medicine, Kyoto University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Miyamoto
authors.forename: A
authors.initials: A
authors.lastname: Matsumori
authors.forename: M W
authors.initials: MW
authors.lastname: Hwang
authors.forename: R
authors.initials: R
authors.lastname: Nishio
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: S
authors.initials: S
authors.lastname: Sasayama
mesh_terms: D000208:Acute Disease; D000818:Animals; D018188:Cardiovirus Infections / Q000150:complications*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004686:Encephalomyocarditis virus; D000068876:Fingolimod Hydrochloride; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009205:Myocarditis / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology*; D009569:Nitric Oxide / Q000032:analysis; D016016:Proportional Hazards Models; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013110:Sphingosine / Q000031:analogs & derivatives; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D011409:Propylene Glycols; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine