Effects of oral clenbuterol on the clinical and inflammatory response to endotoxaemia in the horse.

This research investigates how the drug clenbuterol, taken orally, influences the clinical and inflammatory responses of horses to endotoxin, a common trigger of systemic inflammation. The findings demonstrated that clenbuterol significantly reduced peak rectal temperature and plasma TNFα concentration, suggesting the drug’s potential in countering inflammation caused by low-dose endotoxin.

Background

• The systemic inflammatory response that occurs in horses when exposed to endotoxins is characterized by the activation of leukocytes and endothelial cells. This is majorly directed by pro-inflammatory cytokines, including IL-1β and TNFα.
• β2 agonist drugs like clenbuterol have been identified for their ability to inhibit leukocyte activation. This function has prompted researchers to study the effects of these drugs on endotoxin-induced inflammation in horses.

Methodology

• This research followed a randomized crossover design where horses were administered either clenbuterol or a placebo before exposing them to a low dose of endotoxin. The endotoxin was administered at 30 ng/kg over 30 minutes.
• The team monitored clinical signs in horses, conducted leukocyte count, and gathered serial blood samples over a 6 hour period.

Findings

• The study found that pre-treatment with oral clenbuterol (at a dose of 0.8 μg/kg) significantly reduced both the peak rectal temperature and the peak plasma TNFα concentration following endotoxin exposure. The reduction in rectal temperature and TNFα concentration was noted with P-values of 0.046 and 0.026 respectively, indicating statistical significance.

Implications

• The findings from this study suggest that orally administered clenbuterol could potentially serve as an effective anti-inflammatory treatment for horses experiencing endotoxin-induced inflammation. The drug showed efficacy even at the therapeutic dose when used for a low dose endotoxin challenge.
• The significant effect on peak rectal temperature and plasma TNFα also points towards the ability of clenbuterol to counteract key physiological and molecular aspects of the inflammatory response. This underlines the potential therapeutic benefits that clenbuterol can offer in managing systemic inflammation, especially those provoked by endotoxins, in horses.