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

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_2α, 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_2α 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_2α 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.