Interferon-gamma-inducible protein-10 is associated to increased primary bile acids and fibrosis in primary sclerosing cholangitis.

16/06/2026

The Journal of steroid biochemistry and molecular biology

Authors: Bettina Langhans, Leona Dold, Taotao Zhou, Jacob S Trägner, Silvia Friedrichs, Frans Stellaard, Dieter Lütjohann, Christian P Strassburg, Sandra Kalthoff

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts. Altered bile acid (BA) profile was shown to trigger immune responses in the liver, contributing to inflammation and liver fibrosis. Here, we analyzed BAs, their precursors (oxysterols), surrogate markers of cholesterol synthesis as well as of absorption, and studied their association with clinical/ immunological parameters in PSC. We analyzed concentrations of BAs (cholic acid, CA; chenodeoxycholic acid, CDCA; deoxycholic acid, DCA; lithocholic acid, LCA; ursodeoxycholic acid, UDCA), their precursors (7α-, 24-, 27-hydroxycholesterol, 7αOH-Chol, 24OH-Chol, 27OH-Chol), cholesterol synthesis marker lathosterol and cholesterol absorption markers (5α-cholestanol, sitosterol, campesterol) in serum from patients with PSC (n = 33) in comparison to healthy blood donors (n = 30). Inflammatory cytokines in serum were measured using flow-cytometry-based bead array. While serum concentrations of cholesterol and its precursor lathosterol were comparable between patients with PSC and healthy individuals, serum concentrations of CA and CDCA were statistically significant increased in PSC. Furthermore, we observed elevated concentrations of cholesterol absorption markers in PSC. Association with clinical parameters revealed a statistically significant correlation of CA, CDCA, and cholesterol absorption markers with AP, bilirubin, AST, and ALT. In addition, pro-inflammatory IP-10 (interferon-gamma-inducible protein-10) was increased in serum of PSC patients and associated with primary BAs and liver fibrosis. Our findings reveal a distinct metabolic signature in PSC characterized by increased primary BAs and cholesterol absorption markers in serum. The correlations between IP-10, BAs, and fibrosis suggest a bile acid-driven pro-inflammatory circuit potentially contributing to disease progression.

PMID: 42303059