Authors: Salinas Constanza, Barriga Kassandra, Albornoz Alejandro, Alarcon Pablo, Quiroga John, Uberti Benjamín, Sarmiento José, Henriquez Claudio, Ehrenfeld Pamela, Burgos Rafael A, Moran Gabriel
Journal: Frontiers in veterinary science
Summary
# Editorial Summary Severe equine asthma involves excessive neutrophil extracellular trap (NET) formation—sticky, web-like structures that trap pathogens but also perpetuate airway inflammation—yet tamoxifen, a selective estrogen receptor modulator already used off-label in equine practice for inflammatory airway disease, has shown clinical benefit despite unclear mechanisms. Researchers incubated peripheral blood neutrophils from five healthy horses with tamoxifen at physiologically relevant concentrations and measured NET formation via cell-free DNA quantification, immunofluorescence microscopy, NET morphotype classification, and mitochondrial reactive oxygen species detection. At 10 μM concentration, tamoxifen significantly induced NET formation, predominantly generating spread NETs (95%) with minimal aggregated NETs (5%), potentially via mitochondrial oxidative stress pathways. Paradoxically, this suggests tamoxifen's clinical anti-inflammatory effects in horses with airway disease operate through neutrophil modulation mechanisms *other than* NET suppression—possibly by dampening degranulation, chemotaxis, or other destructive neutrophilic functions—meaning practitioners using this drug for asthma may need to reconsider the biological basis of its efficacy. In vivo studies comparing NET formation in bronchoalveolar lavage fluid from asthmatic versus healthy horses treated with tamoxifen remain essential before confidently attributing clinical improvements to specific immunological pathways.
Read the full abstract on PubMed
Practical Takeaways
- •Tamoxifen may be therapeutically beneficial for horses with severe asthma through mechanisms other than NET suppression; in vivo studies in affected horses are needed to confirm clinical utility
- •Understanding tamoxifen's effects on equine neutrophil function could inform treatment protocols for inflammatory airway disease, though this remains experimental
- •Current evidence is limited to laboratory work on healthy horses; clinical application requires further investigation in naturally-occurring disease
Key Findings
- •Tamoxifen at 10 µM concentration induced neutrophil extracellular trap (NET) formation in equine peripheral blood samples
- •Tamoxifen-induced NETs comprised 95% spread NETs and 5% aggregated NETs
- •Mitochondrial reactive oxygen species (ROS) may influence tamoxifen-induced NET formation
- •Anti-inflammatory effects of tamoxifen in equine airway inflammation are likely due to inhibition of other neutrophilic functions rather than NET formation