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

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_H1) to T_H2 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_H1 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_H1 to T_H2.