title: CTLA4-Ig relieves inflammation in murine models of coxsackievirus B3-induced myocarditis.
abstract: BACKGROUND
  T-cell-mediated cellular immunity is one of the most important factors in viral myocarditis. As an important costimulatory molecule, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) alleviates autoimmunity by influencing the balance of helper T cell (T(H)) subtype 1 (T(H)1) to T(H)2 in autoimmune diseases. The effects and mechanisms of CTLA4 fusion protein (CTLA4-Ig) in mice with coxsackievirus B3 (CVB3)-induced myocarditis were investigated.
  
  
  METHODS
  BALB/c mice were randomly divided into a CVB3 group, an IgG group, a CTLA4-Ig group, and a group of healthy control mice. Mice were humanely killed on day 7 post CVB3 inoculation, then CVB3, IFN-γ, mouse IL-4 (mIL-4), and mouse IL-2 (mIL-2) expression in myocardium were examined by real-time quantitative polymerase chain reaction, and the serum concentrations of IFN-γ, mIL-4, and mIL-2 were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  IFN-γ expression was significantly higher and mIL-4 levels in serum were lower in the CVB3 group when compared with those in the healthy control group (P < 0.01). In the CTLA4-Ig group, the mouse mortality and CVB3 mRNA in myocardium were reduced compared with those in the CVB3 group. Furthermore, IFN-γ expression was lower, and mIL-4 was significantly higher compared with those values in the CVB3 and the IgG groups. The levels of mIL-2 in all groups showed no statistical difference (P > 0.05).
  
  
  CONCLUSIONS
  T(H)1 cytokines were predominant in the acute phase of viral myocarditis. CTLA4-Ig relieves myocardial inflammation, virus replication, and mouse mortality, probably by influencing the balance of T(H)1 to T(H)2.
authors.affiliation: Division of Cardiology, Department of Pediatrics, Provincial Hospital Affiliated to Shandong University, Jinan, China. hanbo35@163.com
authors.forename: Bo
authors.initials: B
authors.lastname: Han
authors.forename: Honglei
authors.initials: H
authors.lastname: Jiang
authors.forename: Zhenhu
authors.initials: Z
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lijian
authors.initials: L
authors.lastname: Zhao
authors.forename: Kang
authors.initials: K
authors.lastname: Lu
authors.forename: Junfang
authors.initials: J
authors.lastname: Xi
mesh_terms: D000818:Animals; D015551:Autoimmunity; D060908:CTLA-4 Antigen / Q000627:therapeutic use*; D003384:Coxsackievirus Infections / Q000150:complications / Q000628:therapy*; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D029822:Enterovirus B, Human; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007155:Immunologic Factors / Q000627:therapeutic use*; D007249:Inflammation / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology / Q000628:therapy*; D009206:Myocardium / Q000276:immunology / Q000473:pathology
chemical_list: D060908:CTLA-4 Antigen; D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors