Effects of Methotrexate on Plasma Cytokines and Cardiac Remodeling and Function in Postmyocarditis Rats

Abstract

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.

Methotrexate attenuates the Th17/IL-17 levels in peripheral blood mononuclear cells from healthy individuals and RA patients

“…Gerards et al examined the whole blood of RA patients and found that MTX dose dependently inhibited the levels of IL-4, IL-13, IFN-c, TNF-a, and GM-CSF that were induced by antibodies to CD3 and CD28. In postmyocarditis rats, MTX also reduced the plasma levels of TNF-a and IL-6 [24]. In this study, we observed in vitro that MTX inhibited IL-17 production at the mRNA and protein levels in PBMCs that had been stimulated with antibodies to CD3 and CD28.…”

Echocardiographic Evaluation of Asymptomatic Patients Affected by Rheumatoid Arthritis

“…A recent experimental study on rats suggests that low-dose methotrexate has the ability to regulate inflammatory responses and improves cardiac function and, hence, contributes to prevent the development of postmyocarditis dilated cardiomyopathy 32 ; this hypothesis could explain the association between LV systolic function and methotrexate assumption.…”

Targeting the Immune System With Pharmacotherapy in Schizophrenia

“…The anti-inflammatory effects of methotrexate appear be at least partly mediated via an increase in adenosine [57]. Adenosine inhibits macrophage activation, and treatment with methotrexate has resulted in decreased levels of TNF-α and IL-6 in-vivo [57, 59, 60]. The outcome of the methotrexate trial will be particularly interesting given the immunomodulatory properties of the drug as well as the adenosine hypothesis of schizophrenia, which lends further theoretical support to its therapeutic potential [61].…”