Evaluation of polymyxin B in an ex vivo model of endotoxemia in horses.

The study conducted tests on the effects of the antibiotic polymyxin B sulfate (PMB) on horses’ response to the toxin produced by bacteria, focusing particularly on its potential role in reducing inflammation. The findings suggest that PMB is safe and can effectively inhibit the inflammation caused by endotoxins in healthy horses.

Study Design and Methods

• The research involved testing on 8 healthy horses. This study followed a crossover design, in which three different doses of PMB (100, 1,000, and 10,000 U/kg of body weight) and a saline solution as a control were evaluated.
• Blood samples were collected both before and after PMB administration for use in two assays: the endotoxin-induced tumor necrosis factor (TNF) assay and the residual endotoxin activity assay.
• The blood samples were incubated with Escherichia coli or Salmonella Typhimurium endotoxins for the TNF assay. The plasma was then harvested and analysed. For the residual endotoxin activity assay, plasma collected in the borosilicate tubes was diluted and incubated before adding more endotoxins. This process was followed by the limulus ameobocyte lysate assay.
• Finally, the researchers monitored the levels of serum creatinine in the horses’ blood for a week. Elevated levels of this waste product could signal kidney dysfunction, providing an additional indicator of the treatment’s potential side effects.

Key Findings

• Use of PMB resulted in a significant reduction in endotoxin-induced TNF activity in a manner dependent on both the administered dose and time passed since administration.
• Administration of 10,000 U/kg of PMB resulted in a significant reduction in residual endotoxin activity as compared to baseline levels.
• It was determined that 1,000 and 5,000 U/kg of PMB could effectively inhibit 75% of endotoxin-induced TNF activity for 3 and 12 hours respectively.
• There was no observable increase in serum creatinine levels, which remained within the reference range, suggesting that PMB administration didn’t harm the horses’ kidney function.

Conclusion

• The research concludes that polymyxin B sulfate can effectively inhibit the inflammation caused by endotoxins in horses. The findings also suggest a level of dose- and time-dependency for the drug’s effectiveness, providing valuable information for further investigations on the optimal dosage and administration schedule for PMB in endotoxemia treatment.