The mechanisms of neurotoxicity induced by unconjugated bilirubin (UCB) in newborns are incompletely understood. UCB may cause both necrotic and apoptotic neuronal death. We explored UCB toxicity and release of cytokines in human NT2-N neurons and the effect of dexamethasone on these processes. Cultured NT2-N neurons were exposed to UCB, and neuronal damage was evaluated by LDH release and MTT cleavage. After 96 hours, 2 μM UCB significantly increased release of IL-8 and MCP-1, but not IL-13, IP-10, PDGF, or VEGF. Dexamethasone significantly lowered the UCB-induced increase in MCP-1 release, and attenuated UCB-induced neuronal damage assessed with MTT cleavage and LDH release. For comparison, the effects of hydrogen peroxide on cytokine formation and neuronal damage were tested. Hydrogen peroxide increased MCP-1, IP-10, and VEGF, but not IL-8, IL-13, or PDGF. Dexamethasone inhibited the hydrogen peroxide-induced increase in MCP-1 and IP-10. We conclude that UCB causes release of IL-8 and MCP-1 in cultured human NT2-N neurons. Dexamethasone reduces UCB-induced cytokine release and protects against UCB-induced toxicity.
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