{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337837/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337837"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Macrophage-Derived IL-18 Drives M1 Polarization via IFN-γ/JAK1-STAT1 Axis to Promote Myocardial Injury in Fulminant Myocarditis","description":"Fulminant myocarditis (FM) is a rapid, severe form of myocarditis requiring urgent mechanistic insight. While anti-interleukin-18 (IL-18) antibodies show promise in other inflammatory diseases, IL-18’s role in FM remains unknown. Here, we found that plasma IL-18 levels in FM patients negatively correlated with ejection fraction and positively with NT-proBNP. Elevated IL-18 was confirmed in a coxsackievirus B3 (CVB3)-induced murine FM model, with macrophages identified as the primary cellular source. Exogenous IL-18 promoted M1 macrophage polarization without affecting cardiomyocytes or fibroblasts. Neutralizing IL-18 antibodies (IL-18nAbs) suppressed M1 polarization and chemokine secretion in vitro, and improved survival, reduced myocardial M1 infiltration, and preserved cardiac function in vivo. Mechanistically, IL-18 activated the JAK1-STAT1 axis in macrophages; STAT1 silencing abrogated IL-18-driven M1 polarization. IL-18 also induced IFN-γ, and IFN-γ neutralization blocked Stat1 and Nos2 upregulation. Myeloid-specific IL-18R1 deletion alleviated CVB3-induced cardiac dysfunction and inflammation. Collectively, IL-18, primarily from macrophages, drives FM progression via JAK1-STAT1, representing a key pathogenic factor and therapeutic target.","dates":{"publication":"2026/07/08"},"accession":"GSE337837","cross_references":{"GSM":["GSM9861239","GSM9861238","GSM9861240","GSM9861243","GSM9861242","GSM9861241"],"GPL":["18480"],"GSE":["337837"],"taxon":["Mus musculus"]}}