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

The research investigates the effect of a synthetic hormone known as altrenogest on the immune system of non-pregnant mares (female horses). It concludes that this hormone alters the immune response both systemically and within the local endometrial environment, and more studies are essential to determine how it affects the immune pathways and subsequent consequences.

Overview of the Research

• The research is focused on the impact of a synthetic hormone called altrenogest (ALT), which is a type of progestin, on the immune system of non-pregnant mares.
• The study also explores how different concentrations of progesterone (P4), a naturally occurring progestin, and ALT affect the production of IFNγ, a type of interferon, commonly known as an immune response modifier, and the expression of specific cytokines, proteins secreted by cells that modulate the activity of the immune system.

Methodologies

• Peripheral blood mononuclear cells (PBMCs), a type of blood cell that plays a critical role in the immune system, from diestrous (non-breeding phase) mares were incubated with varied concentrations of P4 and ALT.
• In-vivo and in-vitro methods were adopted. Ten mares received either ALT or a vehicle control (VEH) daily. The team applied a switchback design, which involved alternating between different treatments, from the ovulation day, continuing for seven days.
• Analysis of circulating PBMCs and endometrial biopsies was conducted to assess the production and expression of the same interferon and cytokines.

Findings and Conclusion

• In vitro, both P4 and ALT caused a dose-dependent decrease in intracellular IFNγ in PBMCs. Also, P4 led to a reduction in the expression of IFNγ, IL-10, and IL-4 in PBMCs, whereas ALT triggered an increase in the expression of IL-6 and IL-1β.
• In vivo, ALT likewise suppressed the intracellular levels of IFNγ in PBMCs on the sixth day. Though control mares experienced a decrease in IL-1β expression from day 0 to day 6, ALT-treated mares did not.
• Locally, within the endometrium, ALT increased the expression of IL-1RN (an anti-inflammatory cytokine) and IFNγ compared to VEH-treated mares.
• The study suggests that both P4 and ALT appear to modify the immune system of the non-pregnant mare, necessitating further research to fully understand how this synthetic progestin influences the immune system of the horse and its potential consequences.