CTLA4-Ig relieves inflammation in murine models of coxsackievirus B3-induced myocarditis

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.

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.

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).

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.