IL-18 in heart failure and SCD. (A) Control of IL-18 and Kv 4.x channels by β-adrenergic signaling (β-AR/GPCR) via CaMKIIδ and NF-κB pathways. These pathways inhibit expression of KCNIP2 (the gene for chaperon protein for Kv 4.2) and KCND3 (the gene for Kv 4.3). (B) Role of IL-18 in promoting arrhythmias and fibrosis in SCD cardiomyopathy. The adverse effects of IL-18 can be counteracted in the murine model by the treatment with IL-18bp for 4 weeks. APD, action potential duration. Professional illustration by ScEYEnce Studios.