Enhanced IL-6 transcriptional response to adenosine receptor ligands in horses with lower airway inflammation.
Authors: Zhang L, Franchini M, Wehrli Eser M, Dip R
Journal: Equine veterinary journal
Summary
# Editorial Summary: Adenosine Signalling and Lower Airway Inflammation in Horses Extracellular adenosine accumulation drives inflammatory responses in human asthma, yet its role in equine airways remained unexplored until this investigation. Eight horses with varying degrees of lower airway disease and ten healthy controls underwent bronchoalveolar lavage (BAL) analysis, with researchers using quantitative RT-PCR to map adenosine receptor (AR) subtype expression and ex vivo cell stimulation to assess IL-6 production—a key inflammatory marker—in response to AR ligands. Cells from compromised airways showed significantly enhanced IL-6 upregulation when exposed to the non-selective agonist NECA, whilst healthy controls showed minimal response; notably, blocking the A₂ₐ receptor subtype with SCH-58261 further amplified IL-6 induction in diseased animals, with the magnitude of this effect correlating directly to airway neutrophil counts. Although all groups expressed predominantly A₂ᵦ receptors with lower A₂ₐ levels, the differential inflammatory signalling suggests that A₂ₐ receptors actively suppress pro-inflammatory IL-6 responses—a compensatory mechanism that appears compromised in airway disease. These findings identify a novel adenosine/IL-6 inflammatory axis in equine lower respiratory disease, pointing toward selective adenosine receptor antagonism as a potential anti-inflammatory therapeutic strategy worthy of further development and clinical evaluation.
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Practical Takeaways
- •Adenosine signalling pathways represent a novel therapeutic target for modulating lower airway inflammation in horses with equine asthma or recurrent airway obstruction
- •Selective A(2A) adenosine receptor antagonists may enhance anti-inflammatory responses in airway-compromised horses and warrant further investigation as potential treatments
- •Future clinical trials should evaluate adenosine receptor ligands as adjunctive therapies for managing equine lower airway disease, particularly in cases with elevated neutrophilic inflammation
Key Findings
- •BAL cells from airway-compromised horses showed upregulated IL-6 expression in response to NECA (nonselective adenosine agonist), whereas control horses showed no change
- •A(2B) adenosine receptor was the predominant subtype expressed in BAL cells, with lower A(2A) levels and marginal A(3) expression
- •Blockade of A(2A) AR with SCH-58261 enhanced IL-6 mRNA induction by NECA in both groups, with higher response in airway-compromised horses correlating with neutrophil count
- •An adenosine/IL-6 inflammatory axis exists in the bronchoalveolar milieu of airway-compromised horses, supporting adenosine receptor targeting as a therapeutic strategy