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

Abstract

REASONS FOR PERFORMING STUDY: Research has shown that 6&#x2009;h 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 6&#x2009;h 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 &#xd7; 10(9) nonviable spermatozoa and 1) no additional treatment (control), or in combination with 2) dexamethasone (50&#x2009;mg i.v.) at the time of insemination, or 3) with mycobacterial cell wall extract (1.5&#x2009;ml i.v.) administered 24&#x2009;h prior to insemination. Mares received one treatment per cycle in randomised order, and each mare served as her own control. Endometrial biopsies were collected 6&#x2009;h after breeding, and quantitative polymerase chain reaction analysis for interleukin (IL)1&#x3b2;, IL6, interferon &#x3b3;, 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 IL1&#x3b2; 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 IL1&#x3b2; 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.