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

Margo L. Macpherson; Steeve Giguère; Malgorzata A. Pozor; Chelsie A. Burden; Londa J. Berghaus; Roy D. Berghaus; Jennifer C. Varner; Justin T. Hayna; Susanne M. Benson; Sarah A. Randell; Sara K. Lyle; Audrey A. Kelleman; Kelsey A. Hart; Martha F. Mallicote; David W. Horohov

doi:10.1111/aji.13396

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

Margo L. Macpherson, Steeve Giguère, Malgorzata A. Pozor, Chelsie A. Burden, Londa J. Berghaus, Roy D. Berghaus, Jennifer C. Varner, Justin T. Hayna, Susanne M. Benson, Sarah A. Randell, Sara K. Lyle, Audrey A. Kelleman, Kelsey A. Hart, Martha F. Mallicote, David W. Horohov

Veterinary Science

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

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_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.

Original language	English
Article number	e13396
Journal	American Journal of Reproductive Immunology
Volume	86
Issue number	1
DOIs	https://doi.org/10.1111/aji.13396
State	Published - Jul 2021

Bibliographical note

Funding Information:
This work was generously funded by the Grayson-Jockey Club Research Foundation. Additional support came from the Kentucky Thoroughbred Owners & Breeders Foundation, Merial Animal Health, a division of Boehringer Ingelheim and the University of Florida, College of Veterinary Medicine. This work was possible due to the tireless efforts of the University of Florida Macpherson Student Research Team who diligently observed and cared for the mares and foals that were essential to this project.

Funding Information:
This work was generously funded by the Grayson‐Jockey Club Research Foundation. Additional support came from the Kentucky Thoroughbred Owners & Breeders Foundation, Merial Animal Health, a division of Boehringer Ingelheim and the University of Florida, College of Veterinary Medicine. This work was possible due to the tireless efforts of the University of Florida Macpherson Student Research Team who diligently observed and cared for the mares and foals that were essential to this project.

Publisher Copyright:
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

anti-inflammatory
cytokine
equine
firocoxib
placentitis
pregnancy
prostaglandin

ASJC Scopus subject areas

Immunology and Allergy
Immunology
Reproductive Medicine
Obstetrics and Gynecology

Access to Document

10.1111/aji.13396

Cite this

Macpherson, M. L., Giguère, S., Pozor, M. A., Burden, C. A., Berghaus, L. J., Berghaus, R. D., Varner, J. C., Hayna, J. T., Benson, S. M., Randell, S. A., Lyle, S. K., Kelleman, A. A., Hart, K. A., Mallicote, M. F., & Horohov, D. W. (2021). Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis. American Journal of Reproductive Immunology, 86(1), [e13396]. https://doi.org/10.1111/aji.13396

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title = "Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis",

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, PGF2α, 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 PGF2α 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 PGF2α 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",

author = "Macpherson, {Margo L.} and Steeve Gigu{\`e}re and Pozor, {Malgorzata A.} and Burden, {Chelsie A.} and Berghaus, {Londa J.} and Berghaus, {Roy D.} and Varner, {Jennifer C.} and Hayna, {Justin T.} and Benson, {Susanne M.} and Randell, {Sarah A.} and Lyle, {Sara K.} and Kelleman, {Audrey A.} and Hart, {Kelsey A.} and Mallicote, {Martha F.} and Horohov, {David W.}",

note = "Funding Information: This work was generously funded by the Grayson-Jockey Club Research Foundation. Additional support came from the Kentucky Thoroughbred Owners & Breeders Foundation, Merial Animal Health, a division of Boehringer Ingelheim and the University of Florida, College of Veterinary Medicine. This work was possible due to the tireless efforts of the University of Florida Macpherson Student Research Team who diligently observed and cared for the mares and foals that were essential to this project. Funding Information: This work was generously funded by the Grayson‐Jockey Club Research Foundation. Additional support came from the Kentucky Thoroughbred Owners & Breeders Foundation, Merial Animal Health, a division of Boehringer Ingelheim and the University of Florida, College of Veterinary Medicine. This work was possible due to the tireless efforts of the University of Florida Macpherson Student Research Team who diligently observed and cared for the mares and foals that were essential to this project. Publisher Copyright: {\textcopyright} 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd",

year = "2021",

month = jul,

doi = "10.1111/aji.13396",

language = "English",

volume = "86",

number = "1",

}

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', American Journal of Reproductive Immunology, vol. 86, no. 1, e13396. https://doi.org/10.1111/aji.13396

TY - JOUR

T1 - Evidence for anti-inflammatory effects of firocoxib administered to mares with experimentally induced placentitis

AU - Macpherson, Margo L.

AU - Giguère, Steeve

AU - Pozor, Malgorzata A.

AU - Burden, Chelsie A.

AU - Berghaus, Londa J.

AU - Berghaus, Roy D.

AU - Varner, Jennifer C.

AU - Hayna, Justin T.

AU - Benson, Susanne M.

AU - Randell, Sarah A.

AU - Lyle, Sara K.

AU - Kelleman, Audrey A.

AU - Hart, Kelsey A.

AU - Mallicote, Martha F.

AU - Horohov, David W.

N1 - Funding Information: This work was generously funded by the Grayson-Jockey Club Research Foundation. Additional support came from the Kentucky Thoroughbred Owners & Breeders Foundation, Merial Animal Health, a division of Boehringer Ingelheim and the University of Florida, College of Veterinary Medicine. This work was possible due to the tireless efforts of the University of Florida Macpherson Student Research Team who diligently observed and cared for the mares and foals that were essential to this project. Funding Information: This work was generously funded by the Grayson‐Jockey Club Research Foundation. Additional support came from the Kentucky Thoroughbred Owners & Breeders Foundation, Merial Animal Health, a division of Boehringer Ingelheim and the University of Florida, College of Veterinary Medicine. This work was possible due to the tireless efforts of the University of Florida Macpherson Student Research Team who diligently observed and cared for the mares and foals that were essential to this project. Publisher Copyright: © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

PY - 2021/7

Y1 - 2021/7

N2 - 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, PGF2α, 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 PGF2α 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 PGF2α 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.

AB - 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, PGF2α, 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 PGF2α 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 PGF2α 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.

KW - anti-inflammatory

KW - cytokine

KW - equine

KW - firocoxib

KW - placentitis

KW - pregnancy

KW - prostaglandin

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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