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

Reasons for performing study: Research has shown that 6 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 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 x 10(9) nonviable spermatozoa and 1) no additional treatment (control), or in combination with 2) dexamethasone (50 mg i.v.) at the time of insemination, or 3) with mycobacterial cell wall extract (1.5 ml i.v.) administered 24 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 h after breeding, and quantitative polymerase chain reaction analysis for interleukin (IL)1 beta, IL6, interferon gamma, 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 beta 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 beta 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.