IL1RAP Blockade With a Monoclonal Antibody Reduces Cardiac Inflammation and Preserves Heart Function in Viral and Autoimmune Myocarditis | Circulation: Heart Failure
BACKGROUND: Currently, there are no therapies targeting specific pathogenic pathways in myocarditis. IL (interleukin)-1 blockade has shown promise in preclinical studies and case reports. We hypothesized that blockade of IL1RAP (IL-1 receptor accessory protein), a shared subunit of the IL-1, IL-33, and IL-36 receptors, could be more efficient than IL-1 blockade alone. METHODS: We induced coxsackievirus B3 (CVB3)–mediated or experimental autoimmune myocarditis (EAM) in BALB/c mice, followed by treatment with an Fc (fragment crystallizable)-modified mIgG2a mouse anti-mouse IL1RAP monoclonal antibody (mCAN10). Myocarditis severity and immune infiltration were assessed by histology and flow cytometry. Cardiac function was measured by echocardiography. We used spatial transcriptomics (Visium 10× Genomics) to compare the gene expression landscape in the hearts of mCAN10-treated versus control mice. RESULTS: IL1RAP blockade reduced CVB3 and EAM severity. In EAM, the treatment prevented deteri
