Lipopolysaccharide infusion up-regulates hepcidin mRNA expression in equine liver.

This research explores how the introduction of lipopolysaccharide (LPS) influences the gene expression of hepcidin—a key hormone regulating iron metabolism—in horses. It found that the infusion of LPS increased hepcidin mRNA expression in the liver, resulting in lower iron concentration in the blood (hypoferremia), thus pointing to hepcidin’s potential role as an acute-phase reactant in horses.

Research Background

• The research focuses on understanding the role of hepcidin in iron metabolism, specifically how it contributes to hypoferremia during inflammation.
• Prior studies have located the primary expression of equine hepcidin to the liver of horses. This research aimed to understand how this expression is affected by the infusion of LPS—components found in the outer membrane of certain bacteria.

Methodology

• Six healthy horses were involved in the study. The team examined the expression of the hepcidin gene in the horses’ liver and bone marrow after infusing Escherichia coli O55:B5 LPS.
• They also examined the IL-6 gene expression in the liver and bone marrow samples, as the inflammatory cytokine is thought to be involved in the process.
• Biopsies were taken before the LPS infusion (to establish a baseline) and at 6 and 18 hours post-infusion. Clinical and lab evaluations were also carried out between 0 and 240 hours post-infusion.

Key Findings

• Results indicated that after LPS infusion, all horses showed signs of endotoxemia, which is a condition that results from the release of endotoxins in the blood.
• After 8 Hours post-infusion, plasma iron concentration had decreased significantly from the pre-infusion level and reached its lowest at 12 Hours. By 30 hours post-infusion, the levels had normalized.
• The study also found a surge in liver hepcidin and IL-6 mRNA expression in the liver 6 hours post-infusion. However, the LPS infusion had no effect on the hepcidin expression in the bone marrow.
• A separate experiment featured equine monocyte cultures stimulated with LPS, which also induced a significant increase in hepcidin and IL-6 gene expression.

Conclusion

• The research concludes that LPS infusion triggers an upsurge in hepatic hepcidin mRNA expression in horses. This increase leads to lowered iron levels in the blood (hypoferremia).
• This finding suggests that hepcidin in horses could potentially serve as an acute-phase protein that responds to inflammation or injury.