Cardioimmunology of Myocarditis: Targeting the IL-1 Pathway

PURPOSE OF REVIEW: Myocarditis is a heterogeneous inflammatory syndrome with aetiologies ranging from viral infection and drug hypersensitivity to systemic autoimmune/autoinflammatory disease and immune checkpoint inhibitor (ICI) therapy. In response to these triggers, the innate immune response and inflammasome activation can amplify myocardial injury via IL-1, providing a mechanistic rationale for IL-1 pathway inhibition as a targeted therapeutic strategy. This review synthesizes preclinical and clinical evidence for IL-1 blockade in myocarditis and related inflammatory cardiac syndromes. RECENT FINDINGS: The immune system plays a central role in the pathogenesis of myocarditis, both in idiopathic/viral cases and in systemic autoimmune and autoinflammatory diseases (SAAD). Interleukin-1 (IL-1) has emerged as a key mediator linking inflammation to myocardial dysfunction, supported by experimental and translational evidence implicating activation of the NLRP3 inflammasome. Clinically, the randomized trial of anakinra in acute myocarditis (ARAMIS) did not improve outcomes in a largely low-risk cohort, but accumulating case reports and small series suggest potential benefit in fulminant/hyperinflammatory myocarditis and chronic active refractory myocarditis. In contrast, IL‑1 inhibitors have robust randomized and real-world evidence in recurrent pericarditis, supporting a myo‑pericardial inflammatory continuum and validating IL‑1 pathway engagement as an actionable target in selected inflammatory cardiac phenotypes. Together, these findings support the evolving concept of cardioimmunology. Current management of myocarditis remains largely supportive, with limited disease-modifying options. Anti-IL-1 therapies, particularly anakinra, have shown promising efficacy in selected severe and refractory cases, with a favourable safety profile. However, evidence is mainly derived from case reports and small series, and robust randomized data are lacking. Key clinical questions remain unresolved, including patient selection, timing of initiation, and treatment duration. Future studies should focus on identifying inflammatory endotypes and evaluating targeted immunomodulatory strategies, including in emerging settings such as ICI-associated myocarditis in which IL‑1 blockade remains investigational.