Effects of methotrexate on plasma cytokines and cardiac remodeling and function in postmyocarditis rats.
Excessive immune activation and inflammatory mediators may play a critical role in the pathogenesis of chronic heart failure. Methotrexate is a commonly used anti-inflammatory and immunosuppressive drug. In this study, we used a rat model of cardiac myosin-induced experimental autoimmune myocarditis to investigate the effects of low-dose methotrexate (0.1 mg/kg/d for 30 d) on the plasma level of cytokines and cardiac remodeling and function. Our study showed that levels of tumor necrosis factor-(TNF-)alpha and interleukin-6 (IL-6) are significantly increased in postmyocarditis rats, compared with the control rats. Methotrexate treatment reduced the plasma levels of TNF-alpha and IL-6 and increased IL-10 level, compared to saline treatment. In addition, postmyocarditis rats showed significant cardiac fibrosis characterized by increased myocardial collagen volume fraction, perivascular collagen area, and the ratio of collagen type I to type III, compared with the control rats. However, MTX treatment not only markedly attenuated cardiac fibrosis, diminished the left ventricular end-diastolic dimension, but also increased the left ventricular ejection fraction and fractional shortening. Collectively, these results suggest that low-dose methotrexate has ability to regulate inflammatory responses and improves cardiac function and hence contributes to prevent the development of postmyocarditis dilated cardiomyopathy.
Zhang
Zhengang
Z
Department of Cardiovascular Disease, The First People's Hospital of Yangzhou, 45 Taizhou Road, Yangzhou, Jiangsu 225001, China. zhzg@yzcn.net
Zhao
Pei
P
Li
Aihua
A
Lv
Xiaolei
X
Gao
Yang
Y
Sun
Hongguang
H
Ding
Yongling
Y
Liu
Jian
J
D000818:Animals; D024042:Collagen Type I / Q000097:blood; D024061:Collagen Type III / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D006321:Heart / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D009205:Myocarditis / Q000188:drug therapy*; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D020257:Ventricular Remodeling
D024042:Collagen Type I; D024061:Collagen Type III; D016207:Cytokines; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008727:Methotrexate