We further revealed that A20 was critical for anti-inflammation and therapeutic effect of AST-IV in myocarditis, evidenced by fewer inflammatory cells infiltration, better survival conditions and improved cardiac function in A20 overexpressed mice with low dose AST-IV (20 mg/kg) treatment following CVB3 infection, in contrast, more sever cardiac inflammation, lower survival rates and worsen cardiac function in A20 knock down mice even with high dose AST-IV (40 mg/kg) treatment. This evidence concerns the gene TNFAIP3 and myocarditis.