Effects of a “two-hit” model of organ damage on the systemic inflammatory response and development of laminitis in horses.

This research examines whether systemic inflammation and organ damage become worse when an animal experiences repeated inflammatory events, using horses as the model. Some horses were exposed to a toxin and others were given a saline treatment, with both groups additionally receiving a specific sugar compound. The study aimed to determine whether sequential exposure to these compounds increased the risk and severity of a horse hoof disease called laminitis.

Research Aim and Hypothesis

• The main objective of this research was to investigate the roles of endotoxemia (presence of toxins in the blood) and systemic inflammation in the development of laminitis, a painful hoof disease in horses.
• The researchers used the “two-hit” sepsis model, a pattern where sequential exposure to inflammatory stimuli potentially amplifies the immune response and the resulting inflammatory impact.
• The hypothesis was that laminitis might occur more frequently and severely when various inflammatory events magnify systemic inflammation and organ damage.

Methodology

• Twenty-four horses with unrelated chronic diseases or behavioral abnormalities were involved in the study, all of which were destined for euthanasia due to these conditions.
• The horses were split into two groups. One group received an eight-hour intravenous infusion of lipopolysaccharide, a toxin known to cause inflammation, while the other received a saline solution.
• Each horse was then given oligofructose, a common sugar compound, via a nasogastric tube.
• The horses were monitored for the development of laminitis, with tissue collection and euthanasia carried out once laminitis reached Obel Grade 2, or after 48 hours if no laminitis had developed.

Results and Findings

• Both the lipopolysaccharide and saline treatments resulted in increased mean rectal temperature, heart rate, respiratory rate, and blood levels of an inflammatory molecule IL-1β. However, the responses were not more intense in the toxin-exposed group.
• 63% of horses in both groups developed laminitis, showing no difference in induction rates between the two groups.
• Upon categorizing horses as laminitis responders and non-responders, it was found that blood IL-1β levels and liver and lung gene expression of several types of interleukins and tumor necrosis factor-α were higher in responders following the administration of oligofructose.
• This suggests that although the pre-treatment with endotoxin did not enhance responses to oligofructose, systemic inflammation was more pronounced in horses that did develop laminitis compared to those that didn’t.
• Further, tissue-generated inflammatory responses could present a higher risk than those actually produced by circulating white blood cells.