EXPERIMENTAL STUDY
Therapeutic effects of FTY720, a new immunosuppressive agent, in a murine model of acute viral myocarditis
Tadashi Miyamoto, MDa,
Akira Matsumori, MD, PhD, FACCa,
Myung-Woo Hwang, MD, PhDa,
Ryosuke Nishio, MD, PhDa,
Haruyasu Ito, MDa and
Shigetake Sasayama, MD, PhD, FACCa
a Department of Cardiovascular Medicine, Kyoto University, Kyoto, Japan
Manuscript received October 10, 2000;
revised manuscript received January 12, 2001,
accepted January 29, 2001.
Reprint requests and correspondence: Dr. Akira Matsumori, Department of Cardiovascular Medicine, Kyoto University, 54 Kawaracho Shogoin, Sakyo-ku, Kyoto 606-8397, Japan amat{at}kuhp.kyoto-u.ac.jp
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.
|
Abbreviations and Acronyms
| | CsA | = cyclosporine A | | EMCV | = encephalomyocarditis virus | | FTY | = FTY720 | | IFN | = interferon | | iNOS | = inducible NO synthase | | NO | = nitric oxide | | TNF | = tumor necrosis factor |
|
This article has been cited by other articles:

|
 |

|
 |
 
J.-R. Nofer, M. Bot, M. Brodde, P. J. Taylor, P. Salm, V. Brinkmann, T. van Berkel, G. Assmann, and E. A.L. Biessen
FTY720, a Synthetic Sphingosine 1 Phosphate Analogue, Inhibits Development of Atherosclerosis in Low-Density Lipoprotein Receptor Deficient Mice
Circulation,
January 30, 2007;
115(4):
501 - 508.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Fujii, T. Kanai, Y. Nemoto, S. Makita, S. Oshima, R. Okamoto, K. Tsuchiya, T. Totsuka, and M. Watanabe
FTY720 suppresses CD4+CD44highCD62L- effector memory T cell-mediated colitis
Am J Physiol Gastrointest Liver Physiol,
August 1, 2006;
291(2):
G267 - G274.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Brinkmann, M. D. Davis, C. E. Heise, R. Albert, S. Cottens, R. Hof, C. Bruns, E. Prieschl, T. Baumruker, P. Hiestand, et al.
The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate Receptors
J. Biol. Chem.,
June 7, 2002;
277(24):
21453 - 21457.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|