Treatment of IL-18-binding protein biologics to treat liver disease
Enhanced interleukin-18 (IL-18) signaling is observed in metabolic dysfunction-associated steatohepatitis (MASH), a chronic liver disease characterized by inflammation and fibrosis.
IL-18-binding protein (IL-18BP) neutralizes IL-18, but its therapeutic potential in MASH is well understood.
In MASH patients and mice the authors found elevated IL-18BP and IL-18 levels with free IL-18 correlating with disease severity. IL-18 stimulates interferon-gamma (IFNγ) production in CD4 T cells and IL-18BP-deficient mice show worsened liver inflammation and fibrosis.
The engineered long acting IL-18BP biologics, APB-R3, displays anti-inflammatory and -fibrosis effect via regulation of IFN signaling and hepatic stellate cell activation via the cGMP pathway.
Treatment of IL-18BP biologics is an attractive strategy to cure MASH injuries.
https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00120-X
