Effects of tamoxifen on the immune response phenotype in equine peripheral blood mononuclear cells.
Authors: Rodríguez Maksimiano, Quiroga John, Cortés Bayron, Morán Gabriel, Henríquez Claudio
Journal: Frontiers in veterinary science
Summary
Tamoxifen's emerging role in equine immunotherapy has prompted investigation into its mechanisms of action, particularly regarding adaptive immunity, though previous research has focused primarily on innate immune effects. Researchers cultured peripheral blood mononuclear cells from healthy horses and exposed them to escalating tamoxifen concentrations, measuring expression of key polarisation genes (TBX21, IFNG, GATA3, IL4, IL10, FOXP3, CTLA4) under stimulated and unstimulated conditions whilst simultaneously assessing regulatory T cell populations. At clinically relevant doses, tamoxifen produced no meaningful changes in lymphocyte gene expression or Treg proportions; only at suprapharmacological concentrations did the drug suppress Th2- and regulatory-associated genes (GATA3, IL4, IL10, CTLA4), though this coincided with substantial cytotoxicity. These findings suggest that tamoxifen's reported benefits in equine asthma-like conditions are unlikely mediated through adaptive immune modulation, implying the drug's therapeutic effects in vivo probably derive from neutrophil-level changes rather than T cell reprogramming. For equine practitioners considering tamoxifen in immune-mediated conditions, this in vitro evidence points toward mechanisms independent of lymphocyte polarisation, warranting caution against assumptions regarding adaptive immune modification and emphasising the need for further clinical investigation to determine whether observed clinical responses reflect off-target effects or alternative immunological pathways.
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Practical Takeaways
- •Tamoxifen's previously reported benefits in equine asthma-like conditions are not explained by changes in T cell polarization or regulatory T cell populations at therapeutic doses
- •Any immune modulation from tamoxifen in horses likely occurs through innate immune mechanisms (neutrophils) rather than adaptive immunity pathways
- •Current evidence does not support using tamoxifen specifically for immune-mediated conditions based on adaptive immune response modulation
Key Findings
- •Tamoxifen at low concentrations did not significantly affect expression of immune polarization genes (TBX21, IFNG, GATA3, IL4, IL10, FOXP3, CTLA4) or regulatory T cell proportions in equine PBMCs
- •At highest concentrations, tamoxifen altered expression of GATA3, IL4, IL10, and CTLA4 genes associated with Th2 and regulatory responses, but only coincided with significant cytotoxicity beyond pharmacological therapy doses
- •The immunomodulatory effects attributed to tamoxifen in preclinical asthma studies in horses likely do not result from modification of the adaptive immune response