Omics · study · 2026
Macrophage-Derived IL-18 Drives M1 Polarization via IFN-γ/JAK1-STAT1 Axis to Promote Myocardial Injury in Fulminant Myocarditis
Listed in NCBI GEO
Fulminant myocarditis (FM) is a rapid, severe form of myocarditis requiring urgent mechanistic insight.
Description
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.
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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.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE337nnn/GSE337837 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE337837 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1491327 ncbi.nlm.nih.gov/bioproject/PRJNA1491327 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Heart 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE337837 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |