IL-1 Signaling Blockade in Human Lymphocytic Myocarditis

Lymphocytic myocarditis is characterized by infiltration of lymphocytes and macrophages. Current treatment for lymphocytic myocarditis is limited to corticosteroids and a proportion of patients progress to require heart transplantation or durable mechanical circulatory support within a year. Increasing attention is directed toward targeting pro-inflammatory mediators in myocarditis. One promising candidate is IL-1. Here, we investigated a patient with underlying autoimmune disease and biopsy confirmed lymphocytic myocarditis who was initially treated with corticosteroids and experienced clinical deterioration requiring temporary mechanical circulatory support. Rilonacept was consequently administered as a salvage therapy. Pathologically, rilonacept reduced inflammation and fibrosis. We performed spatial transcriptomics (ST) on formalin-fixed paraffin-embedded endomyocardial biopsy samples to further investigate how the cardiac immune landscape is modulated by rilonacept. We performed spatial transcriptomics (ST) on formalin-fixed paraffin-embedded endomyocardial biopsy samples to further investigate how the cardiac immune landscape is modulated by rilonacept.