Cytokine production, glutamate release and cell death in rat cultured astrocytes treated with unconjugated bilirubin and LPS

In hyperbilirubinemic newborns, sepsis is considered a risk factor for kernicterus. Evidence shows that injury to astrocytes triggers cytokine release. We examined the effects of unconjugated bilirubin (UCB) alone, or in combination with LPS, on the release of glutamate and cytokines from astrocytes in conditions inducing less than 10% of cell death. UCB leads to an increase of extracellular glutamate and highly enhances the release of TNF-α and IL-1β, while inhibiting the production of IL-6. LPS potentiates immunostimulatory properties of UCB. These results point out the role of cytokines and provide a basis for the significance of sepsis in UCB encephalopathy.