Problem: Progestins are immunomodulatory in a variety of species. In the horse, the most commonly administered synthetic progestin is altrenogest (ALT), but its effect on the immune system of the non-pregnant mare is unknown. Methods: Peripheral blood mononuclear cells (PBMCs) from diestrous mares were incubated with varying concentrations of progesterone (P4) or ALT to assess intracellular production of IFNγ and the expression of select cytokines. Additionally, ten mares received either ALT or VEH daily utilizing a switchback design beginning on the day of ovulation and continuing for 7 days. Circulating PBMCs and endometrial biopsies were obtained to assess the production and expression of the same cytokines. Results: In vitro, both P4 and ALT caused a dose-dependent decrease in intracellular IFNγ in PBMCs. P4 caused a dose-dependent decrease in the expression of IFNγ, IL-10 and IL-4, while ALT caused an increase in the expression of IL-6 and IL-1β in PBMCs. In vivo, ALT suppressed the intracellular levels of IFNγ in PBMCs on d6. While control mares experienced a decrease in IL-1β expression from d0 to d6, ALT-treated mares did not. In the endometrium, ALT increased the expression of IL-1RN and IFNγ in comparison with VEH-treated mares. Conclusion: P4 and ALT appear to alter the immune system of the non-pregnant mare both systemically in addition to locally within the endometrium. Further research is necessary to determine the pathways through which this synthetic progestin functions on the immune system of the horse, and the consequences it may have.
|Journal||American Journal of Reproductive Immunology|
|State||Published - Aug 2019|
Bibliographical noteFunding Information:
The authors would like to thank Staci Sherman and Morgan Reece for their assistance with this project. This work was funded in part by the Albert G. Clay Endowment of the University of Kentucky, the Lincoln Memorial University College of Veterinary Medicine, and the John P. Hughes Endowment at the University of California‐Davis.
The authors would like to thank Staci Sherman and Morgan Reece for their assistance with this project. This work was funded in part by the Albert G. Clay Endowment of the University of Kentucky, the Lincoln Memorial University College of Veterinary Medicine, and the John P. Hughes Endowment at the University of California-Davis.
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
- glucocorticoid receptor
- peripheral blood mononuclear cell
ASJC Scopus subject areas
- Immunology and Allergy
- Reproductive Medicine
- Obstetrics and Gynecology