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Cytokine- and endotoxin-enhanced bilirubin cytotoxicity
1Department of Paediatrics, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
Aim:
To determine the effects of endotoxin and cytokines on the cytotoxic effects of bilirubin.
Methods:
A cell-culture model was developed to simulate the effect of an infection by adding endotoxin from E. coli (LPS) and pro-inflammatory cytokines (TNF-alpha, IL-Ialpha, IL-1beta, and IL-6) to the medium. The cytotoxic effects were measured by a modified MTT method. Four cell lines were tested; they were neuroblastoma, glioblastoma, liver, and endothelial cells.
Results:
Both endotoxin and pro-inflammatory cytokines were demonstrated to enhance bilirubin cytotoxicity on all the cell lines tested, as illustrated by endothelial cell from umbilical vein. Endotoxin and TNF-alpha also showed an additive effect. TNF-alpha concentrations at much lower than clinical sepsis levels have been shown to produce significant cytotoxic effects.
Conclusion:
We speculate that in the jaundiced neonate, infection may increase the risk of tissue damage or kernicterus.