{"doi":"10.1161/atvbaha.123.320382","title":"Inhibition of IL-1 Ameliorates Cardiac Dysfunction and Arrhythmias in a Murine Model of Kawasaki Disease","abstract":"BACKGROUND: Kawasaki disease (KD) is an acute febrile illness and systemic vasculitis often associated with cardiac sequelae, including arrhythmias. Abundant evidence indicates a central role for IL (interleukin)-1 and TNFα (tumor necrosis factor-alpha) signaling in the formation of arterial lesions in KD. We aimed to investigate the mechanisms underlying the development of electrophysiological abnormalities in a murine model of KD vasculitis. METHODS: Lactobacillus casei cell wall extract–induced KD vasculitis model was used to investigate the therapeutic efficacy of clinically relevant IL-1Ra (IL-1 receptor antagonist) and TNFα neutralization. Echocardiography, in vivo electrophysiology, whole-heart optical mapping, and imaging were performed. RESULTS: KD vasculitis was associated with impaired ejection fraction, increased ventricular tachycardia, prolonged repolarization, and slowed conduction velocity. Since our transcriptomic analysis of human patients showed elevated levels of both IL-1β and TNFα, we asked whether either cytokine was linked to the development of myocardial dysfunction. Remarkably, only inhibition of IL-1 signaling by IL-1Ra but not TNFα neutralization was able to prevent changes in ejection fraction and arrhythmias, whereas both IL-1Ra and TNFα neutralization significantly improved vasculitis and heart vessel inflammation. The treatment of L casei cell wall extract–injected mice with IL-1Ra also restored conduction velocity and improved the organization of Cx43 (connexin 43) at the intercalated disk. In contrast, in mice with gain of function of the IL-1 signaling pathway, L casei cell wall extract induced spontaneous ventricular tachycardia and premature deaths. CONCLUSIONS: Our results characterize the electrophysiological abnormalities associated with L casei cell wall extract–induced KD and show that IL-1Ra is more effective in preventing KD-induced myocardial dysfunction and arrhythmias than anti-TNFα therapy. These findings support the advancement of clinical trials using IL-1Ra in patients with KD.","journal":"Arteriosclerosis Thrombosis and Vascular Biology","year":2024,"id":431417,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9654,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":644325,"name":"Yen‐Nien Lin","orcid":"0000-0002-9899-2137","position":1,"is_corresponding":false},{"id":33509,"name":"Shuang Chen","orcid":"0000-0002-2919-4967","position":2,"is_corresponding":false},{"id":640243,"name":"Youngho Lee","orcid":"0000-0002-5227-683X","position":3,"is_corresponding":false},{"id":948473,"name":"Rodrigo Miguel‐dos‐Santos","orcid":"0000-0001-8839-3416","position":4,"is_corresponding":false},{"id":873956,"name":"Asli E. Atici","orcid":"0000-0003-1546-7191","position":5,"is_corresponding":false},{"id":390154,"name":"Michael C. Fishbein","orcid":"0000-0002-6591-6306","position":6,"is_corresponding":false},{"id":231571,"name":"Magali Noval Rivas","orcid":"0000-0001-5570-8928","position":7,"is_corresponding":false},{"id":231575,"name":"Moshe Arditi","orcid":"0000-0001-9042-2909","position":8,"is_corresponding":false},{"id":317255,"name":"Eugenio Cingolani","orcid":"0000-0001-5939-8111","position":9,"is_corresponding":false},{"id":317250,"name":"Thássio Mesquita","orcid":"0000-0002-6927-5745","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T01:59:25.642507Z","pmid":"38385289","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}