Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis.
Abstract: 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. 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 PGE 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. 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 PGE concentrations were lower in FIRO than INFECT. Amniotic PGF and PGE 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. Data suggest a suppressive effect of firocoxib administration on cytokine and prostaglandin production in mares with placentitis.
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Publication Date: 2021-02-10 PubMed ID: 33569862DOI: 10.1111/aji.13396Google Scholar: Lookup
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Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research paper focuses on investigating the anti-inflammatory effects of firocoxib, a veterinary drug, on horses (mares) with experimentally induced placentitis, a condition of inflamed placenta. The study underscores the lack of existing evidence to guide therapy decisions for equine placentitis, aiming to fill that research gap.
Objectives and Methods
- The primary objective of the research was to assess the effectiveness of firocoxib in reducing inflammation among mares with placentitis.
- The study involved grouping mares (around 270-300 days into pregnancy) into three categories for studying different scenarios: those with untreated placentitis (INFECT), those with placentitis treated with firocoxib (FIRO), and healthy control mares without infection or treatment (NORM).
- Data for the research was extracted from allantoic fluid, collected 8 hours, 24 hours, and at birth after infection, and amniotic fluid obtained at birth.
- Concentrations of particular substances, including IL-1β, IL-6, TNF-α, IL-10, PGF, and PGE, known markers of inflammation, were measured using the ELISA technique. Also, the mRNA expression of these substances, along with matrix metalloproteinases (MMPs) -1, 3, and 9 in fetal membranes and fetuses was quantified using real-time PCR, a technique to amplify and measure DNA.
Key Findings
- Allantoic TNF-α concentrations were lowest in the FIRO group 8 hours and 24 hours post-infection when compared with the INFECT group.
- IL-6 concentrations, key indicators of inflammation, were comparably lower in the firocoxib-treated group (FIRO) compared to the other groups at different time intervals post-infection.
- The cytokine levels in the amniotic fluid were lowest in the NORM group with all measurements being below the limit of detection, expectedly in line with the non-infected and untreated nature of the group.
- PGF and PGE concentrations, involved in the inflammatory response, followed a similar trend, with lower levels in the FIRO group compared to the INFECT group. In the INFECT group, these concentrations were higher than in the NORM group.
- The research also underscores that differences in the levels of IL-1β, IL-6, IL-8, and MMP1 in fetal membranes varied depending on the tissue type.
Conclusion
- Overall, the study concludes that firocoxib shows a suppressive effect on cytokine and prostaglandin – key markers of inflammation – production in mares with placentitis, thereby indicating its potential effectiveness as an anti-inflammatory therapeutic option for equine placentitis.
Cite This Article
APA
Macpherson ML, Giguère S, Pozor MA, Burden CA, Berghaus LJ, Berghaus RD, Varner JC, Hayna JT, Benson SM, Randell SA, Lyle SK, Kelleman AA, Hart KA, Mallicote MF, Horohov DW.
(2021).
Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis.
Am J Reprod Immunol, 86(1), e13396.
https://doi.org/10.1111/aji.13396 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
- Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
- Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA.
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
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