Interleukin‐6 pathobiology in equine placental infection

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.