Blocking the CD40–CD40L interaction by CD40-Ig reduces disease progress in murine myocarditis induced by CVB3

Introduction nd CD40L, as costimulatory molecules, are reported to play a critical role for cytokine production and antigen-specific T-cell activation in acute viral myocarditis (VMC). The purpose of this study was to probe the therapeutic effect of CD40-Ig in coxsackievirus B3 (CVB3)-induced myocarditis. s cent male Balb/c mice were infected with cardiovirulent CVB3 and then injected with CD40-Ig (0.1 mg/kg) at 6 h and 3 days postinfection (pi), with IgG (0.1 mg/kg) as control. The surviving mice were sacrificed on the seventh day. The copies of CVB3 mRNA in the myocardium were detected by real-time PCR and the expression of CD40 protein and CD4+ T cell was assessed by immunohistochemistry method. The serum level of IL-4 and IFN-γ and their transcriptions in the myocardium were determined by ELISA and real-time PCR. s rtality was low in VMC model mice receiving CD40-Ig treatment with relived inflammation and reduced transcription of CVB3 in the myocardium. The expression pattern of IFN-γ (Th1-related cytokine) and IL-4 (Th2-related cytokine) was altered to Th1 prevalence in the acute phase of VMC. Intervention of CD40-Ig switched the balance of Th1/Th2. sions ndings suggest that intervention of CD40-Ig can relieve the myocardial injury and inhibit viral replication of CVB3 in VMC. Its mechanism may involve blocking the interaction between CD40 and CD40L and regulating the Th1/Th2 balance.