Viral myocarditis (VMC) is a common disease characterized by cardiac inflammation. AC-73, an inhibitor of CD147, disrupts the dimerization of CD147, which participates in the regulation of inflammation. To explore whether AC-73 could alleviate cardiac inflammation induced by CVB3, mice were injected intraperitoneally with AC-73 on the fourth day post-infection (dpi) and sacrificed on the seventh dpi. Pathological changes in the myocardium, T cell activation or differentiation, and expression of cytokines were analyzed using H&E staining, flow cytometry, fluorescence staining and multiplex immunoassay. The results showed that AC-73 alleviated cardiac pathological injury and downregulated the percentage of CD45+CD3+ T cells in the CVB3-infected mice. The administration of AC-73 reduced the percentage of activated CD4+ and CD8+ T cells (CD69+ and/or CD38+) in the spleen, while the percentage of CD4+ T cell subsets in the spleen was not changed in the CVB3-infected mice. In addition, the infiltration of activated T cells (CD69+) and macrophages (F4/80+) in the myocardium also decreased after the AC-73 treatment. The results also showed that AC-73 inhibited the release of many cytokines and chemokines in the plasma of the CVB3-infected mice. In conclusion, AC-73 mitigated CVB3-induced myocarditis by inhibiting the activation of T cells and the recruitment of immune cells to the heart. Thus, CD147 may be a therapeutic target for virus-induced cardiac inflammation.
Keywords: CD147; T cell activation; Th cell subsets; anti-inflammation; viral myocarditis.