The effect of treatment with immune modulators on endometrial cytokine expression in mares susceptible to persistent breeding-induced endometritis

TY - JOUR

T1 - The effect of treatment with immune modulators on endometrial cytokine expression in mares susceptible to persistent breeding-induced endometritis

AU - Woodward, E. M.

AU - Christoffersen, Mette

AU - Horohov, D.

AU - Squires, E. L.

AU - Troedsson, M. H. T.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Reasons for performing study: Research has shown that 6h after breeding is a critical time during the uterine innate immune response, and the failure to respond appropriately will result in persistent breeding-induced endometritis. This presents a potential opportunity to modulate the course of inflammation towards a timely resolution. Objectives: To evaluate the effects of immune modulation on endometrial mRNA expression of inflammatory genes in susceptible mares 6h after breeding. The hypothesis was that immune modulation alters endometrial cytokine expression in susceptible mares. Study design: A randomised controlled study to evaluate the effects of mycobacterial cell wall extract and dexamethasone on endometrial gene expression after insemination in 6 mares susceptible to persistent breeding-induced endometritis. Methods: Six susceptible mares were selected based on their uterine inflammatory response to insemination. Mares were inseminated during 3 oestrous cycles with 1 × 109 nonviable spermatozoa and 1) no additional treatment (control), or in combination with 2) dexamethasone (50mg i.v.) at the time of insemination, or 3) with mycobacterial cell wall extract (1.5ml i.v.) administered 24h prior to insemination. Mares received one treatment per cycle in randomised order, and each mare served as her own control. Endometrial biopsies were collected 6h after breeding, and quantitative polymerase chain reaction analysis for interleukin (IL)1β, IL6, interferon γ, IL10 and IL1RA was performed. Relative quantification values reported fold changes in mRNA expression from the control. Data were analysed using an ANOVA and significance was set at P<0.05. Results: Expression of IL1β mRNA was lower after treatment with dexamethasone (P<0.001) and mycobacterial cell wall extract (P<0.05) when compared with control. No differences were detected in the mRNA expression of the other cytokines after any of the treatments. Conclusions: Treatment with immune modulators alters endometrial mRNA expression of IL1β after insemination. A better understanding of the mechanisms of immune modulation in the equine uterus can help to improve treatments for persistent breeding-induced endometritis.

AB - Reasons for performing study: Research has shown that 6h after breeding is a critical time during the uterine innate immune response, and the failure to respond appropriately will result in persistent breeding-induced endometritis. This presents a potential opportunity to modulate the course of inflammation towards a timely resolution. Objectives: To evaluate the effects of immune modulation on endometrial mRNA expression of inflammatory genes in susceptible mares 6h after breeding. The hypothesis was that immune modulation alters endometrial cytokine expression in susceptible mares. Study design: A randomised controlled study to evaluate the effects of mycobacterial cell wall extract and dexamethasone on endometrial gene expression after insemination in 6 mares susceptible to persistent breeding-induced endometritis. Methods: Six susceptible mares were selected based on their uterine inflammatory response to insemination. Mares were inseminated during 3 oestrous cycles with 1 × 109 nonviable spermatozoa and 1) no additional treatment (control), or in combination with 2) dexamethasone (50mg i.v.) at the time of insemination, or 3) with mycobacterial cell wall extract (1.5ml i.v.) administered 24h prior to insemination. Mares received one treatment per cycle in randomised order, and each mare served as her own control. Endometrial biopsies were collected 6h after breeding, and quantitative polymerase chain reaction analysis for interleukin (IL)1β, IL6, interferon γ, IL10 and IL1RA was performed. Relative quantification values reported fold changes in mRNA expression from the control. Data were analysed using an ANOVA and significance was set at P<0.05. Results: Expression of IL1β mRNA was lower after treatment with dexamethasone (P<0.001) and mycobacterial cell wall extract (P<0.05) when compared with control. No differences were detected in the mRNA expression of the other cytokines after any of the treatments. Conclusions: Treatment with immune modulators alters endometrial mRNA expression of IL1β after insemination. A better understanding of the mechanisms of immune modulation in the equine uterus can help to improve treatments for persistent breeding-induced endometritis.

U2 - 10.1111/evj.12266

DO - 10.1111/evj.12266

M3 - Journal article

C2 - 24645833

SN - 0425-1644

VL - 47

SP - 235

EP - 239

JO - Equine Veterinary Journal

JF - Equine Veterinary Journal

IS - 2

ER -