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  Discussion on Research Summary: Chronic Endometritis and Immunmodulatory Therapy
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DrO

Posted on Monday, Sep 24, 2007 - 12:43 pm:

Here are two great studies that adds a completely new therapy for one of the most frequent and frustrating problems facing breeders: chronic endometritis.

Nonspecific immunomodulatory therapy, like the older products EqStim and ImmunoRegulin, and the newer product SETTLE, use bacterial cell orignin products to stimulate the immune system. The idea is the stimulated immune systen will better be able to fight infection in the uterus and return the endometrium to a more normal histology and what was found in the first study. The next step in the research is doing controlled studies on pregnancy rates and that is exactly what the second paper does show: it was effective for increasing pregnancy rates in mares with chronic endometritis. It is not known if some products might be better than others for this.
DrO

Vet Immunol Immunopathol. 2007 Jul 15;118(1-2):30-9. Epub 2007 May 3.
Immune parameters in mares resistant and susceptible to persistent post-breeding endometritis: effects of immunomodulation.

Fumuso EA, Aguilar J, Giguere S, Rivulgo M, Wade J, Rogan D.

UNICEN, Facultad de Ciencias Veterinarias, Pinto 399, Tandil 7000, Argentina. efumuso@vet.unicen.edu.ar

Our objective was to characterize immune parameters in susceptible (SM) and resistant (RM) mares, with and without artificial insemination (AI) and immunomodulation. Eight RM and eight SM were selected based on their reproductive history and functional tests. Both groups of mares were evaluated during three consecutive cycles: Cycle 1, untreated cycle (control); Cycle 2, AI with dead semen; Cycle 3, AI with dead semen and immunomodulation. Endometrial biopsies were taken during the three cycles as follows: Cycle 1--at estrus, when follicles > or =35mm and at diestrus (7+/-1 days after ovulation); Cycle 2--at estrus 24h post-AI, and at diestrus; Cycle 3--at estrus 24h after treatment with a Mycobacterium phlei cell-wall extract (MCWE) and AI, and at diestrus. The mRNA transcription (mRNAT) of IL-8 and IL-10 were determined by real-time PCR. Image analysis of immunohistochemistry slides was performed using digital software (Image-Pro Plus v 5.0; Media Cybernetics); the percentage of stained area was determined for Major Histocompatibility Complex II (MHC-II), polymorphonuclear leukocytes (PMN) and T lymphocytes (TL) on each tissue section. In Cycle 1, SM had significantly higher MHC-II, TL, PMN and IL-8 than RM during estrus (P<0.006, P<0.0005, P<0.05, respectively), while transcription of IL-10 was significantly lower than in RM (P<0.0001). During diestrus, SM had higher levels of TL, PMN and IL-8 than RM (P<0.0001). After AI (Cycle 2), SM had higher levels of IL-8 and lower levels of IL-10 than RM at estrus and no differences were detected for MHC-II, TL and PMN positive cells. During diestrus in the same cycle, all the immune parameters were higher in SM mares (P<0.005, P<0.0004, P<0.0001, P<0.02, respectively). When MCWE was applied at the time of AI (Cycle 3), SM expressed significant higher levels of IL-10 24h after treatment (P<0.005), which were also higher than in the control Cycle 2 or after AI (Cycle 2). However, no significant differences were detected for MHC-II, lymphocytes-PMN or IL-8 between SM and RM during diestrus in Cycle 3. This study showed that SM had higher levels of all immune parameters except IL-10 than RM during Cycle 1. After AI (Cycle 2), the inflammatory condition persisted in SM but not RM mares until day 7 post-ovulation. Following treatment with MCWE at the time of AI (Cycle 3) uterine immunological changes in SM resulted in an endometrial immune environment similar to that found in normal RM.

J Am Vet Med Assoc. 2007 Jul 1;231(1):107-13.
Effect of adjunctive treatment with intravenously administered Propionibacterium acnes on reproductive performance in mares with persistent endometritis.
Rohrbach BW, Sheerin PC, Cantrell CK, Matthews PM, Steiner JV, Dodds LE.
Department of Comparative Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA.

OBJECTIVE: To determine whether treatment with a preparation of Propionibacterium acnes would improve pregnancy and live foal rates in mares with persistent endometritis. DESIGN: Randomized placebo-controlled clinical trial. ANIMALS: 95 mares with a cytologic diagnosis of persistent endometritis. PROCEDURES: Mares were treated with P acnes or placebo (both administered IV) on days 0, 2, and 6. No attempt was made to alter additional treatments administered by attending veterinarians. Information on breeding history, physical examination findings, results of cytologic examination and microbial culture of uterine samples, additional treatments administered, breeding dates, results of pregnancy examinations, whether a live foal was produced, and reactions to treatment was recorded. RESULTS: In multivariate logistic regression models, mare age, year of entry into the study, and first breeding within 8 days after first treatment with P acnes or placebo were significantly associated with pregnancy. Fewer number of cycles bred and younger age were significantly associated with delivery of a live foal in a separate multivariate analysis. Results of multivariate logistic regression modeling indicated that mares treated with P acnes were more likely to become pregnant and to deliver a live foal, compared with placebo-treated controls. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of P acnes as an adjunct to conventional treatments in mares with a cytologic diagnosis of persistent endometritis improved pregnancy and live foal rates. The optimal effect was detected in mares bred during the interval extending from 2 days before to 8 days after first treatment with P acnes.
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