Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis

Am J Reprod Immunol. 2021 Jul;86(1):e13396. doi: 10.1111/aji.13396. Epub 2021 Feb 10.

Abstract

Problem: Minimal evidence exists supporting therapeutic selections for equine placentitis. The goal of this study was to characterize the anti-inflammatory effects of firocoxib when administered to mares with placentitis.

Methods: Mares (gestation D270-300) were assigned to: INFECT (n = 6; placentitis, no treatment), FIRO (n = 6; placentitis, firocoxib, 0.1 mg/kg, PO, daily), and NORM (n = 6; no infection/treatment). Allantoic fluid (8 hours, 24 hours, birth) and amniotic fluid (birth) were collected from mares after infection. Concentrations of IL-1β, IL-6, TNF-α, IL-10, PGF , and PGE2 in fluids were measured by ELISA. mRNA expression of IL-1β, IL-6, TNF-α, IL-8, IL-10, matrix metalloproteinases (MMPs) -1, 3, and 9 in fetal membranes/fetuses was quantified using real-time PCR.

Results: Allantoic TNF-α concentrations were lowest in FIRO at 8 hours and 24 hours post-infection; IL-6 concentrations were lower in FIRO than NORM at 8 hours, lower in FIRO than INFECT at 24 hours post-inoculation, and lower in NORM than FIRO or INFECT at birth. Marginal mean allantoic IL-β and IL-10 concentrations were lower in FIRO and NORM than INFECT. Amniotic fluid cytokines were lowest in NORM with all measurements in that group being below the limit of detection. Allantoic PGF concentrations were lower in FIRO and INFECT than NORM at 8 hours post-inoculation, and lower in FIRO than INFECT or NORM at 24 hours post-inoculation. Allantoic PGE2 concentrations were lower in FIRO than INFECT. Amniotic PGF and PGE2 concentrations were lower in NORM than INFECT. In fetal membranes, group differences with respect to IL-1β, IL-6, IL-8, and MMP1 were dependent on tissue type.

Conclusions: Data suggest a suppressive effect of firocoxib administration on cytokine and prostaglandin production in mares with placentitis.

Keywords: anti-inflammatory; cytokine; equine; firocoxib; placentitis; pregnancy; prostaglandin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Female
  • Horse Diseases / drug therapy*
  • Horses
  • Inflammation / drug therapy*
  • Interleukin-6 / metabolism
  • Matrix Metalloproteinase 1 / metabolism
  • Placenta / metabolism*
  • Placenta / pathology
  • Placenta Diseases / drug therapy*
  • Pregnancy
  • Prostaglandins / metabolism
  • Sulfones / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cyclooxygenase 2 Inhibitors
  • Interleukin-6
  • Prostaglandins
  • Sulfones
  • Tumor Necrosis Factor-alpha
  • Matrix Metalloproteinase 1
  • 4-Butyrolactone
  • firocoxib