Interleukin-1 and the NLRP3 Inflammasome in Pericardial Disease

Abstract

Purpose of review: Pericarditis is a generally benign disease, although complications and/or recurrences may occur in up to 30% of cases. New evidence on the pathophysiology of the disease has accumulated in recent years.

Recent findings: Recently, it has been shown that the activation of the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein 3) inflammasome is central in the pathophysiology of pericarditis. These findings derive from clinical data, an experimental animal model of acute pericarditis supporting a role for the NLRP3 inflammasome in pericarditis, and from indirect evidence of inhibitors of NLRP3 inflammasome in clinical trials. Pericarditis is regarded as a stereotypical response to an acute damage of the mesothelial cells of the pericardial layers. NLRP3 inflammasome, a macromolecular structure sensing damage and releasing pro-inflammatory cytokines, is centrally involved as it releases interleukin (IL)-1β, whose auto-induction feeds an autoinflammatory disease, mostly responsible for recurrences. Colchicine, an inhibitor of NLRP3 inflammasome formation, and IL-1-targeted therapies, such as anakinra and rilonacept, were found to effectively blunt the acute inflammation and reduce the risk for recurrences.

Keywords: Acute pericarditis; Anakinra; IL-1; NLRP3 inflammasome; Recurrent pericarditis; Rilonacept.