Low‐dose lipopolysaccharide exposure can increase in vivo bilirubin production rates in newborn mice

AIM: Neonatal haemolysis increases bilirubin production rates, which can then lead to severe hyperbilirubinaemia and bilirubin neurotoxicity. During haemolysis, haem is degraded by haem oxygenase (HO), which can be induced under stress conditions. It is known that neonatal sepsis is a risk factor for haemolysis and severe hyperbilirubinaemia. Here, we evaluated whether an exposure to lipopolysaccharide (LPS) to induce sepsis can upregulate HO-1, further increasing in vivo bilirubin production rates in mouse pups under haem loads. METHODS: Three-day-old pups were given LPS (1250 mug/kg) or saline (controls). Liver HO enzyme activity, HO-1 mRNA and HO-1 protein were measured post-LPS exposure. We then assessed the effects of LPS treatment on in vivo bilirubin production rates after haem loading. RESULTS: Liver HO activity significantly increased (142%) over controls 24 hours after treatment with LPS (1250 mug/kg) without mortality. Liver HO-1 mRNA was significantly upregulated 2.47-fold at 24 hours post-LPS administration, while liver HO-1 protein increased 1.29-fold 24 hours post-LPS treatment. After haem loading, pups exposed to LPS had significantly higher bilirubin production rates (1.30-fold) compared with age-matched, saline-treated controls. CONCLUSION: Low-dose LPS treatment can upregulate liver HO-1 expression and may underlie the severe hyperbilirubinaemia seen in septic infants, particularly when undergoing haemolysis.