Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares.
Abstract: The objective of the present study was to evaluate the effect of immunomodulatory therapy (glucocorticoids (GC) and mycobacterium cell wall extract (MCWE)) on the endometrial gene expression of inflammatory cytokines in susceptible mares with induced infectious endometritis. Endometrial gene expression of pro- and anti-inflammatory cytokines; interleukin (IL)-1β, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, IL-1 receptor antagonist (ra), acute phase protein (APP) serum amyloid A (SAA) and clinical parameters were evaluated. Five mares were classified as susceptible to persistent endometritis based on their endometrial histopathology and ability to clear an induced uterine inflammation. To investigate the effect of immunomodulatory therapy, the mares were inoculated with 10(5) colony forming units (CFU) Escherichia coli in three consecutive estrus cycles in a modified cross-over study design. Thus, each mare served as its own control and the treatment type was performed in randomized order. The effect of treatment with MCWE (1.5 mg Settle IV), dexamethasone (0.1 mg per kg IV) or no treatment was investigated. All mares were free from uterine inflammation before each E. coli inoculation. Endometrial biopsies were recovered 3, 24 and 72 h post inoculation. Relative gene-expression analyses were performed by quantitative reverse transcriptase PCR (qRT-PCR). Endometrial gene expression of inflammatory cytokines was modulated by administration of GC. Expression of proinflammatory cytokines (IL-1β, IL-6, IL-8) and SAA was significantly lower in the GC treated group late in the study period (72 h) compared to "no treatment" and MCWE treatment. Increased expression of the anti-inflammatory cytokine IL-10 was observed 3 and 24 h after E. coli infusion and GC treatment. A significant decrease of SAA expression was observed after MCWE treatment compared to "no treatment". MCWE and GC treatment had a significant effect on the clearance of uterine pathogens and number of mares retaining fluid after E. coli infusion. The results of the current investigation suggest that GC is capable of effectively modulating the innate immune response to induced infectious endometritis in susceptible mares.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication Date: 2012-07-21 PubMed ID: 22819284DOI: 10.1016/j.theriogenology.2012.04.016Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study explores the impact of immunomodulatory therapy, specifically using glucocorticoids (GC) and mycobacterium cell wall extract (MCWE), on the inflammation reaction within the endometrium – the lining of the uterus – in mares prone to persistent endometritis, a type of uterine inflammation, induced by E. coli infection.
Experimental Design
- The experiment involved five mares identified as prone to persistent endometritis based on their endometrial histopathology and their ability to clear induced uterine inflammation.
- The mares were infected three times in consecutive estrus (reproductive) cycles with 10^5 colony forming units of Escherichia coli. This cross-over study design allowed each mare to serve as her own control group, and the treatment types were administered in a randomized order.
- Different treatments applied were MCWE, dexamethasone (a type of glucocorticoid), or no treatment. The mares were free of uterine inflammation before each E. coli inoculation.
- Mares’ endometrial biopsies were taken 3, 24, and 72 hours after each E. coli inoculation to evaluate changes in gene expression over time.
Results and Findings
- The pro-inflammatory cytokines and the acute phase protein, SAA, in the endometrium showed significantly lower expression by the end of the study period (72 hours) in the Glucocorticoid (GC) treated group, as compared to the untreated and MCWE-treated groups.
- The study also observed increased expression of anti-inflammatory cytokine IL-10 three hours and 24 hours post-infection in the GC-treated group.
- A significant decrease in the expression of SAA was noted after MCWE treatment as compared to “no treatment”.
- The use of MCWE and GC treatments significantly influenced the clearance of uterine pathogens and reduced the number of mares retaining fluid in the uterus post E. coli infection.
Conclusion
- The findings suggested that glucocorticoids could effectively modulate, alter or control, the innate immune response to induced infectious endometritis in mares susceptible to this condition.
Cite This Article
APA
Christoffersen M, Woodward EM, Bojesen AM, Petersen MR, Squires EL, Lehn-Jensen H, Troedsson MH.
(2012).
Effect of immunomodulatory therapy on the endometrial inflammatory response to induced infectious endometritis in susceptible mares.
Theriogenology, 78(5), 991-1004.
https://doi.org/10.1016/j.theriogenology.2012.04.016 Publication
Researcher Affiliations
- Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. christoffersen75@hotmail.com
MeSH Terms
- Animals
- Anti-Inflammatory Agents / therapeutic use
- Cytokines / genetics
- Cytokines / metabolism
- Dexamethasone / therapeutic use
- Endometritis / drug therapy
- Endometritis / metabolism
- Endometritis / microbiology
- Endometritis / veterinary
- Endometrium / drug effects
- Endometrium / metabolism
- Endometrium / pathology
- Escherichia coli Infections / drug therapy
- Escherichia coli Infections / pathology
- Escherichia coli Infections / veterinary
- Estrous Cycle
- Female
- Gene Expression Regulation / drug effects
- Gene Expression Regulation / physiology
- Horse Diseases / drug therapy
- Horse Diseases / immunology
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Mycobacterium / chemistry
- Reverse Transcriptase Polymerase Chain Reaction
Citations
This article has been cited 11 times.- Nocera FP, Maurizi L, Masullo A, Nicoletti M, Conte AL, Brunetti F, De Martino L, Zagaglia C, Longhi C. Genotypic and Phenotypic Characterization of Escherichia coli Isolates Recovered from the Uterus of Mares with Fertility Problems.. Animals (Basel) 2023 May 14;13(10).
- Tyrnenopoulou P, Fthenakis GC. Clinical Aspects of Bacterial Distribution and Antibiotic Resistance in the Reproductive System of Equids.. Antibiotics (Basel) 2023 Mar 28;12(4).
- Zhao W, Wang J, Li Y, Ye C. Citral protects against LPS-induced endometritis by inhibiting ferroptosis through activating Nrf2 signaling pathway.. Inflammopharmacology 2023 Jun;31(3):1551-1558.
- Katila T, Ferreira-Dias G. Evolution of the Concepts of Endometrosis, Post Breeding Endometritis, and Susceptibility of Mares.. Animals (Basel) 2022 Mar 19;12(6).
- Solano-Suárez G, Caixeta LS, Masic A, Manríquez D, Hatamoto-Zervoudakis L, Paudyal S, Velasquez-Munoz A, Velez J, Pinedo PJ. Effect of peripartal administration of mycobacterium cell wall fraction on health and fertility of Holstein cows under organic-certified management.. J Anim Sci 2021 Sep 1;99(9).
- Segabinazzi LGTM, Canisso IF, Podico G, Cunha LL, Novello G, Rosser MF, Loux SC, Lima FS, Alvarenga MA. Intrauterine Blood Plasma Platelet-Therapy Mitigates Persistent Breeding-Induced Endometritis, Reduces Uterine Infections, and Improves Embryo Recovery in Mares.. Antibiotics (Basel) 2021 Apr 23;10(5).
- Omontese BO, Caixeta LS, Machado VS, Rendahl A, Celestino MLK, Menta PR, Paiva D, Garcia-Muñoz A, Masic A. Effects of the Administration of a Non-specific Immune Stimulant Around Transportation on Health and Performance of Jersey and Jersey-Cross Heifer Calves During the Rearing Period: Randomized Clinical Trial.. Front Vet Sci 2020;7:550202.
- Jana B, Całka J. Endometritis Changes the Neurochemical Characteristics of the Caudal Mesenteric Ganglion Neurons Supplying the Gilt Uterus.. Animals (Basel) 2020 May 20;10(5).
- Canisso IF, Segabinazzi LGTM, Fedorka CE. Persistent Breeding-Induced Endometritis in Mares - a Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology.. Int J Mol Sci 2020 Feb 20;21(4).
- Marth CD, Firestone SM, Glenton LY, Browning GF, Young ND, Krekeler N. Oestrous cycle-dependent equine uterine immune response to induced infectious endometritis.. Vet Res 2016 Nov 8;47(1):110.
- Marth CD, Young ND, Glenton LY, Noden DM, Browning GF, Krekeler N. Deep sequencing of the uterine immune response to bacteria during the equine oestrous cycle.. BMC Genomics 2015 Nov 14;16:934.
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