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

View larger version (14K):
[in a new window]
|
Figure 1 Fourteen-day cumulative survival after encephalomyocarditis virus inoculation in FTY720 treated mice (open circles), versus cyclosporine A-treated mice (filled circles) versus control mice (filled squares).
|
|

View larger version (20K):
[in a new window]
|
Figure 2 Myocardial histopathologic scores for cellular infiltration (A) and necrosis (B) on day 5 after encephalomyocarditis virus inoculation in surviving mice. *p < 0.05; **p < 0.01. CsA = cyclosporine A; FTY = FTY720; NS = not significant.
|
|

View larger version (152K):
[in a new window]
|
Figure 3 Representative photomicrograph of histopathologic sections of the heart. A and D: control mouse; B and E: cyclosporine A-treated mouse; C and F: FTY720-treated mouse. Hematoxylin and eosin stain, A,B,C: original magnification x200, bar = 50 µm, D,E,F: original magnification x2, bar = 1 mm.
|
|

View larger version (12K):
[in a new window]
|
Figure 4 Effects of FTY (FTY720) and cyclosporine A (CsA) on intracardiac virus concentration on day 5 after encephalomyocarditis virus inoculation in surviving mice. *p < 0.05. NS = not significant.
|
|

View larger version (24K):
[in a new window]
|
Figure 5 Intracardiac cytokine protein levels on day 5 after encephalomyocarditis virus inoculation in surviving mice. A: interleukin (IL)-2; B: IL-12; C: interferon (IFN)-gamma; D: tumor necrosis factor (TNF)-alpha. *p < 0.05, **p < 0.01, # p < 0.001. CsA = cyclosporine A; FTY = FTY720; NS = not significant.
|
|

View larger version (12K):
[in a new window]
|
Figure 6 Intracardiac nitric oxide (NO) content on day 5 after encephalomyocarditis virus inoculation in surviving mice. #p < 0.001. CsA = cyclosporine A; FTY = FTY720; NS = not significant.
|
|
|