Suppression of myocardial inflammation using suramin, a growth factor blocker.
Autoimmune myocardial injuries are involved in the pathogenesis of myocarditis and dilated cardiomyopathy, but effective strategies for treating myocardial inflammation have not yet been established. The present study investigated the effects of suramin, a growth factor blocker, on experimental autoimmune myocarditis (EAM) in rats. Lewis rats were immunized with cardiac myosin and placed into one of 4 groups: every 72 h for 1 month the control group (C) was subcutaneously injected with saline; group L received 4mg/kg of suramin; group M, 10 mg/kg: group H, 40 mg/kg. The heart weight/body weight ratios of the M and H groups were significantly lower than that of the C group. Macroscopic and microscopic scores for myocarditis were reduced in the M and H groups. The expression of transforming growth factor (TGF)-beta mRNA in the heart was significantly decreased in the M and H groups compared with the C. In the next experiment, we investigated the effects of suramin on the cytokine milieu in EAM. The serum level of interleukin-10 on day 15 was significantly increased by suramin treatment. Furthermore, suramin increased the number of T cells with Th2 function in the popliteal lymph nodes. Suramin suppressed myocardial inflammation in EAM and was associated with modulation of the Th1/Th2 cytokine milieu and reduced TGF-beta1 expression in the heart.
Shiono
Takaaki
T
First Department of Internal Medicine, Institute of Nephrology, Niigata University School of Medicine, Japan. sio@cocoa.ocn.ne.jp
Kodama
Makoto
M
Hanawa
Haruo
H
Fuse
Koichi
K
Yamamoto
Tadashi
T
Aizawa
Yoshifusa
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000503:physiopathology; D009202:Cardiomyopathies / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000235:genetics; D006131:Growth Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D009205:Myocarditis / Q000276:immunology* / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D013498:Suramin / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006131:Growth Inhibitors; D013498:Suramin