title: Blocking the CD40-CD40L interaction by CD40-Ig reduces disease progress in murine myocarditis induced by CVB3.
abstract: BACKGROUND
  CD40 and 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.
  
  
  METHODS
  Adolescent 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.
  
  
  RESULTS
  The mortality 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.
  
  
  CONCLUSIONS
  Our findings 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.
authors.affiliation: Division of Cardiology, Department of Pediatrics, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China. hanbo35@163.com
authors.forename: Han
authors.initials: H
authors.lastname: Bo
authors.forename: Liu
authors.initials: L
authors.lastname: Zhenhu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Lijian
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000037:antagonists & inhibitors* / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology*; D003384:Coxsackievirus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D004195:Disease Models, Animal; D018450:Disease Progression; D029822:Enterovirus B, Human / Q000235:genetics / Q000472:pathogenicity*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D013997:Time Factors; D014779:Virus Replication
chemical_list: D019013:CD40 Antigens; C499839:CD40Ig protein, recombinant; D012333:RNA, Messenger; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma