Abstract
Cell-mediated immune events play a role in the pathogenesis of myocarditis provoked by Group B coxsackievirus (CVB). Studies indicated the synthetic derivative of androstene-3β,7β,17β-triol, HE3286 (17α-ethynyl-5-androstene-3β,7β,17β-triol), may ameliorate the course of immunoinflammatory and autoimmune diseases in rodents. The aim of this study was to evaluate effects of HE3286 on histological signs of CVB-induced myocarditis. BALB/c mice were infected with coxsackie B3 virus (CB3V) and treated by intraperitoneal administration of dexamethasone (Dex) or by oral gavage with HE3286 or with its vehicle, HERF405, for 18 days. Mice were sacrificed and hearts were explanted for histological and immunohistochemical analysis (TNF-α, IL-6, MMP9, ADAM10 and HSP-70). Heart tissues of Dex-treated mice showed a better histological structure compared with mice treated with HERF405. An almost complete resolution of myocarditis was observed in HE3286-treated mice as evidenced by lack of inflammatory infiltration. Immunohistochemical findings confirmed HE3286 had a more pronounced effect than Dex in reducing inflammatory response associated with in situ modulation of cytokine expression and tissue remodeling. Our data demonstrate HE3286 has better results in inhibiting establishment and progression of murine CVB-induced myocarditis than Dex, suggesting this drug may also have a therapeutic role in treatment of CVB-induced myocarditis.
Highlights
Myocarditis, characterized by inflammation of the myocardium associated with cardiac dysfunction [1,2], is divided into three categories: noninfectious, infectious and that in which the immune mechanism is triggered or maintained by an infection
We evaluated the impact of treatment with HE3286 or Dex in a mouse model of CVB-induced myocarditis and on histological signs of disease and immunohistochemical detection of cytokines of tumor necrosis factor-α (TNF-α), IL-6, MMP9, a disintegrin and metalloprotease-10 (ADAM10) and heat shock protein-70 (HSP-70) involved in molecular mechanisms of cardiomyopathies [15,21,23] and other tissues [24,25,26,27,28]
The histological examination of the heart tissue showed a clear trend toward the resolution of myocarditis in mice treated with HE3286 compared to those treated with vehicle alone and to those treated with Dex, suggesting a benefit from treatment with HE3286
Summary
Myocarditis, characterized by inflammation of the myocardium associated with cardiac dysfunction [1,2], is divided into three categories: noninfectious, infectious and that in which the immune mechanism is triggered or maintained by an infection.
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