Pediatric research

Additive effect of tumor necrosis factor-alpha and endotoxin on bilirubin cytotoxicity.

PMID 10203145


Clinical observations suggest that sepsis may enhance the risk of kernicterus. This study investigated the combined effects of bilirubin, endotoxin, and tumor necrosis factor-alpha (TNF-alpha), which simulate sepsis in a jaundiced mouse fibroblast cell line. The horseradish peroxidase oxidation method was applied for bilirubin-albumin titration studies to test the effect of endotoxin and TNF-alpha on bilirubin-albumin binding. A modified 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide method was used to study cytotoxicity. Bilirubin caused cytotoxicity in a dose-dependent manner in the cultured mouse fibroblasts. Such an effect was significantly amplified by TNF-alpha and endotoxin. TNF-alpha and endotoxin had no effect on the bilirubin-albumin titration curves. Our results have shown that TNF-alpha and endotoxin increase the cytotoxicity of bilirubin. These findings provide supportive evidence that sepsis would increase the risk of tissue damage by bilirubin.