Effects of a MAPK p38 inhibitor on lung function and airway inflammation in equine recurrent airway obstruction.

The research article focuses on the examination of the potential of a compound known as MAPK p38 inhibitor, specifically MRL-EQ1, in treating or preventing recurrent airway obstruction (RAO) in horses, a prevalent and debilitating respiratory condition.

Research Methodology

• The study was divided into two phases – prevention and treatment, where MRL-EQ1 was tested on horses susceptible to RAO.
• In Phase 1, horses in clinical remission were divided into two groups and were exposed to environmental triggers such as stabling, dusty conditions, and moldy hay. The treatment group received MRL-EQ1 for 14 days while the other group remained untreated.
• In Phase 2, horses already suffering from RAO were divided randomly into two groups getting either dexamethasone (a common treatment for RAO) or MRL-EQ1.
• Data was collected on several variables such as bronchoalveolar lavage fluid, respiratory mechanic measurements, MRL-EQ1 plasma concentration, and tumour necrosis factor (TNF) whole blood activity.

Findings

• In Phase 1, MRL-EQ1 was found not to prevent the appearance of clinical signs and lung inflammation, but it significantly reduced the severity of the symptoms and delayed the onset of signs while decreasing pulmonary neutrophilia, indicating decreased inflammation.
• Phase 2, however, showed that it did not improve lung function and airway inflammation for horses who were already experiencing RAO. Moreover, MRL-EQ1 caused behavioural changes such as depression and excitability and led to blood changes including neutrophilia and increased serum muscle enzyme concentrations, suggesting potential side effects.

Conclusions

• The study concludes that the p38 inhibitor was partially effective in reducing clinical signs and airway inflammation when administered to horses before the onset of RAO but was not effective during a clinical exacerbation of the condition.
• However, the potential side-effects mean that p38 inhibitors with a better toxicity profile may be a more effective solution for prevention or treatment of the RAO condition.

The research holds importance for studies aimed at improving treatment options for RAO in horses and suggests a potential area for further research in the exploration of p38 inhibitors with fewer side-effects.