科研之友
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摘要
P>Myocarditis is an inflammation of the myocardium which often follows virus infections. Coxsackievirus B3 (CVB3), as a marker of the enterovirus group, is one of the most important infectious agents of virus-induced myocarditis. Using a CVB3-induced myocarditis model, we show that injection alpha-galactosylceramide (alpha-GalCer), a ligand for invariant natural killer (NK) T (iNK T) cells, can protect the mice from viral myocarditis. After the systemic administration of alpha-GalCer in CVB3 infected mice, viral transcription and titres in mouse heart, sera and spleen were reduced, and the damage to the heart was ameliorated. This is accompanied by a better disease course with an improved weight loss profile. Compared with untreated mice, alpha-GalCer-treated mice showed high levels of interferon (IFN)-gamma and interleukin (IL)-4, and reduced proinflammatory cytokines and chemokines in their cardiac tissue. Anti-viral immune response was up-regulated by alpha-GalCer. Three days after CVB3 infection, alpha-GalCer-administered mice had larger spleens. Besides NK T cells, more macrophages and CD8+ T cells were found in these spleens. Upon stimulation with phorbol myristate acetate plus ionomycin, splenocytes from alpha-GalCer-treated mice produced significantly more cytokines [including IFN-gamma, tumour necrosis factor-alpha, IL-4 and IL-10] than those from untreated mice. These data suggest that administration of alpha-GalCer during acute CVB3 infection is able to protect the mice from lethal myocarditis by local changes in inflammatory cytokine patterns and enhancement of anti-viral immune response at the early stage. alpha-GalCer is a potential candidate for viral myocarditis treatment. Our work supports the use of anti-viral treatment early to reduce the incidence of virus-mediated heart damage.
