Allergen challenge alters lymphocyte phosphodiesterase activity in horses with heaves.

This research investigates the impact of allergens on the activity of phosphodiesterases (PDE) in the lymphocytes of horses suffering from an allergic airway disease known as heaves, by comparing them to healthy horses. The findings suggest that there are differences in how these PDE activities are controlled in horses with the disease.

Introduction

• The study focuses on heaves, an allergic airway disease in horses. The disease is characterized by reversible airway obstruction, bronchial hyperresponsiveness, and airway inflammation. Horses with heaves show a Th(2) response, which is an immune response often associated with allergies and asthma.
• Predominantly, the study explores lymphocyte PDE activity. Lymphocytes are a type of white blood cell vital to the body’s immune response. The functioning of these cells can be regulated by cyclic nucleotide-dependent signaling pathways, meaning they are influenced by molecules like cAMP (Cyclic adenosine monophosphate) and cGMP (Cyclic guanosine monophosphate).
• PDE are enzymes that break down these cyclic nucleotides, thereby influencing the signaling pathways and subsequent lymphocyte activity.

Methodology

• Researchers measured the total PDE activity and the effects of isoenzyme-selective inhibitors in horses suffering from heaves and compared them to healthy control animals.
• The tests were performed before, 5 and 24 hours after a 7-hour long allergen challenge.
• The inhibitors used include those selective for PDE3 (enzyme), PDE4, and PDE5, and non-selective PDE inhibitor.

Results

• It was found that the allergen challenge did not affect total cAMP PDE activity. The inhibition caused by PDE4-selective inhibitor (rolipram) and non-selective inhibitor (theophylline) was also unchanged.
• However, before the allergen challenge, a PDE3 selective inhibitor (quazinone) caused greater inhibition of cAMP PDE activity among heave-susceptible horses.
• Moreover, the total cGMP PDE activity was significantly lower 24 hours after the allergen challenge in the heaves group. The inhibition caused by the PDE5 selective inhibitor decreased in the heaves group at this time.
• The PDE inhibitors seemed to affect the proliferation of immunoactive mononuclear cells. There was a decrease in proliferation after the allergen challenge in the heaves group, unlike the control group. The effect of a combination of PDE3 and PDE5 inhibitor on proliferation was simply additive, despite the differing reactions to allergens.

Conclusion

• The results suggest that lymphocyte PDE activity is differently controlled in horses affected by heaves, possibly due to the impact of the disease on the way lymphocyte function is regulated, through changing PDE related cyclic nucleotide signaling pathways.