Duration of in vivo endotoxin tolerance in horses.

This research focuses on gaining a better understanding of endotoxin tolerance in horses. The researchers find that endotoxin tolerance, a reduced inflammatory response to endotoxins, lasts around one week in horses. The finding is important for designing future studies involving repeated testing on horse subjects since a minimum of three weeks should be allowed between experiments to avoid interference from this tolerance effect.

Objective of the Research

• The study aimed to establish the duration of endotoxin tolerance in horses for the first time. Understanding this duration is vital to the design of repeated measure studies using equine endotoxemia models, as the altered responsiveness from endotoxin tolerance would confound study results.
• In particular, the researchers sought to measure and compare physical, clinicopathologic, and proinflammatory gene expression responses to repeated endotoxin exposures in horses.

Methodology

• This study involved six horses, each of which received three endotoxin exposures at different time intervals.
• Each exposure involved an infusion of lipopolysaccharides (LPS), a component of endotoxin, in saline.
• Pain scores, physical examination parameters, and blood samples for complete blood count and proinflammatory gene expression were obtained at predetermined intervals for 24 hours following each exposure.
• The treatments were administered in a randomized, crossover design to permit balanced, comparative analysis of the tolerance effect.

Results

• The study found that LPS produced clinical and clinicopathologic signs of endotoxemia in horses and increased the expression of certain proinflammatory genes.
• Following a second exposure to LPS after 7 days, horses exhibited signs of endotoxin tolerance, including significantly lower pain scores, heart rates, respiratory rates, and duration of fever compared to first and last exposures.
• However, this tolerance seemed to have subsided by the third exposure 14-21 days later, as clinical parameters and gene expression were similar or slightly increased compared to the first exposure. This suggests the tolerance duration does not extend beyond two weeks.

Conclusion

• The study concludes that horses display an in vivo tolerance to endotoxins which lasts around a week but seems to have waned by two weeks following the initial exposure.
• From this finding, the researchers suggest that a minimum of three weeks should be allowed between experiments if repeated measures designs are used to evaluate the in vivo response to endotoxin in horses.