Cytokine- and endotoxin-enhanced bilirubin cytotoxicity.
OBJECTIVE
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.


CONCLUSIONS
We speculate that in the jaundiced neonate, infection may increase the risk of tissue damage or kernicterus.
Yeung
C Y
CY
Department of Paediatrics, The University of Hong Kong, Queen Mary Hospital, Pokfulam Road, Hong Kong, China.
Ngai
K C
KC
D001663:Bilirubin / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006801:Humans; D007378:Interleukins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004731:Endotoxins; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D001663:Bilirubin