β2 adrenergic activation induces the expression of IL-18 binding protein, a potent inhibitor of isoproterenol induced cardiomyocyte hypertrophy in vitro and myocardial hypertrophy in vivo

► The β-AR agonist isoproterenol induces cardiomyocyte hypertrophy in vitro and in vivo via IL-18. ► Isoproterenol induces the expression of IL-18BP, a neutralizing IL-18 binding protein via β2-AR. ► Isoproterenol induces IL-18BP expression via PI3K/Akt and ERK1/2-dependent CREB and C/EBPβ activation. ► Isoproterenol induced cardiomyocyte hypertrophy is blunted in IL-18BP Tg and IL-18 null mice. ► IL-18BP may have therapeutic potential in the treatment of hypertrophied failing heart.