Effects of the insulin sensitizing drug, pioglitazone, and lipopolysaccharide administration on markers of systemic inflammation and clinical parameters in horses.

This research investigates the effects of the drug pioglitazone on systemic inflammation and clinical parameters in horses, aiming to reduce the risk of laminitis – a condition associated with equine metabolic syndrome (EMS).

Background and Objective

• Equine metabolic syndrome (EMS) is a disease in obese horses, causing insulin resistance, systemic inflammation, and increasing the risk of laminitis – a painful condition affecting horses’ feet.
• The system-wide inflammation seen in EMS is believed to be influenced by inflammatory proteins produced by adipose tissue (body fat).
• The researchers hypothesized that reducing this inflammation could lower the incidence of laminitis in EMS-affected horses.
• The objective of this study was to determine if pre-treatment with pioglitazone, a drug known to reduce obesity-related inflammation in humans, could alleviate the development of inflammation and related clinical markers in horses after administration of Lipopolysaccharide (LPS), a bacterial component known to trigger strong immune responses.

Research Design and Methodology

• The experiment involved 16 adult horses: eight were treated with 1mg/kg of pioglitazone for 14 days, and eight served as controls.
• Several measures were taken before and after the administration of LPS, such as physical examination, testing for hematologic variables, measuring pro-inflammatory cytokines in muscle and adipose tissues, and assessing concentration of the acute phase protein (serum amyloid A) and pro-inflammatory cytokine (TNF-α) in the blood.
• LPS was administered to induce systemic inflammation, replicating the inflammatory processes seen in EMS.

Results

• LPS administration successfully induced systemic inflammation, witnessed by clinical and hematological changes, increased levels of TNF-α, serum amyloid A, and increased IL-6 mRNA abundance in adipose tissue.
• However, the study found no evidence that pre-treatment with pioglitazone mitigated these effects, revealing that it did not reduce inflammation or the clinical markers associated with it.

Conclusions and Future Directions

• The researchers concluded that pioglitazone, at the particular dose and duration tested, did not effectively lessen inflammation nor related clinical signs in horses after LPS administration.
• They suggest the possibility of longer treatment periods or higher dosage for future research to better understand the potential of pioglitazone in treating or preventing laminitis in horses with EMS.