Alteration of the mare's immune system by the synthetic progestin, altrenogest

Carleigh Elizabeth Fedorka, Barry A. Ball, Olivia F. Walker, Alan J Conley, Cynthia J. Corbin, Kristina G. Lu, Jessica M. Hanneman, Mats H.T. Troedsson, Amanda A. Adams

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere13145
JournalAmerican Journal of Reproductive Immunology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Progesterone Congeners
Immune System
Blood Cells
Endometrium
Interleukin-1
Horses
Cytokines
altrenogest
Progestins
Ovulation
Interleukin-4
Interleukin-10
Progesterone
Interleukin-6
Biopsy

Keywords

  • altrenogest
  • cytokine
  • endometrium
  • equine
  • glucocorticoid receptor
  • peripheral blood mononuclear cell
  • progesterone

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

Cite this

Alteration of the mare's immune system by the synthetic progestin, altrenogest. / Fedorka, Carleigh Elizabeth; Ball, Barry A.; Walker, Olivia F.; Conley, Alan J; Corbin, Cynthia J.; Lu, Kristina G.; Hanneman, Jessica M.; Troedsson, Mats H.T.; Adams, Amanda A.

In: American Journal of Reproductive Immunology, 01.01.2019.

Research output: Contribution to journalArticle

Fedorka, Carleigh Elizabeth ; Ball, Barry A. ; Walker, Olivia F. ; Conley, Alan J ; Corbin, Cynthia J. ; Lu, Kristina G. ; Hanneman, Jessica M. ; Troedsson, Mats H.T. ; Adams, Amanda A. / Alteration of the mare's immune system by the synthetic progestin, altrenogest. In: American Journal of Reproductive Immunology. 2019.
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abstract = "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.",
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AU - Fedorka, Carleigh Elizabeth

AU - Ball, Barry A.

AU - Walker, Olivia F.

AU - Conley, Alan J

AU - Corbin, Cynthia J.

AU - Lu, Kristina G.

AU - Hanneman, Jessica M.

AU - Troedsson, Mats H.T.

AU - Adams, Amanda A.

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AB - 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.

KW - altrenogest

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KW - endometrium

KW - equine

KW - glucocorticoid receptor

KW - peripheral blood mononuclear cell

KW - progesterone

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