Work

Inhibitors of the Interleukin-1 Receptor Accessory Protein Signaling: Another Asset in the Cardio-Immunology Toolbox

Year: 2024

Type: editorial

Abstract: Acute myocarditis is a complex syndrome characterized by an inflammatory injury to the myocardium in response to non-ischemic or toxic insults, including infections and auto-immune responses.The prognosis of acute myocarditis is rather variable, ranging from life-threatening conditions in fulminant myocarditis to asymptomatic finding in some cases. 1 It is a widely accepted concept that an exuberant and/or aberrant immune response contribute to the pathogenesis and pathophysiology of acute myocarditis, yet, except for some specific forms of myocarditis like giant cell myocarditis or eosinophilic myocarditis, a clear role of immunomodulating therapies is lacking. 2 The classic form of acute myocarditis is characterized by the presence of myocardial injury in close proximity to activated T lymphocytes, and therefore the interest has mostly focused on the adaptive immune response.An interplay between the adaptive and innate immune responses in myocarditis exists, by which activation of the inflammasome pathway leads to amplification of the immune response and injury in experimental myocarditis models.2 The inflammasome is a macromolecular intracellular structure responsible for the detection of infectious and non-infectious danger signals and the processing of pro-inflammatory cytokines of the Interleukin-1 (IL-1) family of cytokines such as IL-1β and IL-18, leading to local and systemic inflammation.3 Human and mouse data show that components of the NLRP3 (NACHT-, LRR-and pyrin domain-containing protein 3) inflammasome are increased in the hearts of subjects with acute myocarditis.2,4 In an experimental model of acute myocarditis due to enterovirus, the treatment with an IL-1β blocking antibody limited the inflammatory response, interstitial fibrosis, and adverse myocardial remodeling.5 Two independent studies showed that inhibition of the NLRP3 inflammasome, with two different inhibitors in mice or rats, reduces inflammation and myocardial damage in coxsackievirus B3 (CVB3).2,6 Independent assessments looked at the effects of recombinant IL-1 receptor antagonist (IL-1Ra) or the myocardial delivery of an expression vector coding IL-1Ra in the

Source: Circulation Heart Failure

DOI: 10.1161/circheartfailure.124.012244

Authors: Stefano Toldo, Guglielmo Gallone, Antonio Abbate

Institutions: University of Virginia, Azienda Ospedaliera Citta' della Salute e della Scienza di Torino, University of Turin

Language: English

Topic: Viral Infections and Immunology Research

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute