Interleukin-6 pathobiology in equine placental infection

Am J Reprod Immunol. 2021 May;85(5):e13363. doi: 10.1111/aji.13363. Epub 2021 Feb 9.

Abstract

Problem: Ascending placentitis is the leading cause of abortion in the horse. Interleukin (IL)-6 is considered predictive of placental infection in other species, but little is understood regarding its role in the pathophysiology of ascending placentitis.

Method of study: Sub-acute ascending placentitis was induced via trans-cervical inoculation of S zooepidemicus, and various fluids/serum/tissues collected 8 days later. Concentrations of IL-6 were detected within fetal fluids and serum in inoculated (n = 6) and control (n = 6) mares. RNASeq was performed on the placenta (endometrium and chorioallantois) to assess transcripts relating to IL-6 pathways. IHC was performed for immunolocalization of IL-6 receptor (IL-6R) in the placenta.

Results: IL-6 concentrations increased in allantoic fluid following inoculation, with a trend toward an increase in amniotic fluid. Maternal serum IL-6 was increased in inoculated animals, while no changes were noted in fetal serum. mRNA expression of IL-6-related transcripts within the chorioallantois indicates that IL-6 is activating the classical JAK/STAT pathway, thereby acting as anti-inflammatory, anti-apoptotic, and pro-survival. The IL-6R was expressed within the chorioallantois, indicating a paracrine signaling pathway of maternal IL-6 to fetal IL-6R.

Conclusion: IL-6 plays a crucial role in the placental response to induction of sub-acute equine ascending placentitis, and this could be noted in amniotic fluid, allantoic fluid, and maternal serum. Additionally, IL-6 is acting as anti-inflammatory in this disease, potentially altering disease progression, impeding abortion signals, and assisting with the production of a viable neonate.

Keywords: IL-6; JAK/STAT; cytokine; equine; infectious abortion; placentitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amniotic Fluid / immunology
  • Animals
  • Endometrium / immunology
  • Female
  • Horse Diseases / blood
  • Horse Diseases / genetics
  • Horse Diseases / immunology*
  • Horses
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology*
  • Placenta / immunology
  • Placenta Diseases / blood
  • Placenta Diseases / genetics
  • Placenta Diseases / immunology*
  • Placenta Diseases / veterinary
  • Pregnancy
  • Receptors, Interleukin-6 / genetics
  • Receptors, Interleukin-6 / immunology
  • Streptococcal Infections / blood
  • Streptococcal Infections / genetics
  • Streptococcal Infections / immunology*
  • Streptococcal Infections / veterinary
  • Streptococcus equi*

Substances

  • Interleukin-6
  • Receptors, Interleukin-6