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BMC veterinary research2016; 12; 83; doi: 10.1186/s12917-016-0706-8

Characterization and differentiation of equine experimental local and early systemic inflammation by expression responses of inflammation-related genes in peripheral blood leukocytes.

Abstract: Local inflammation may progress into systemic inflammation. To increase our understanding of the basic immunological processes during transition of equine local inflammation into a systemic state, investigation into the equine systemic immune response to local inflammation is warranted. Therefore, the aim of this study was to investigate the innate peripheral blood leukocyte (PBL) immune response to local inflammation in horses, and to compare this response with the PBL immune response during the early phase of acute systemic inflammation. Expression of 22 selected inflammation-related genes was measured in whole blood leukocytes from 6 horses in an experimental cross-over model of lipopolysaccharide- (LPS-) induced acute synovitis (3 μg LPS intraarticularly; locally inflamed [LI] horses) and endotoxemia (1 μg LPS/kg intravenously; systemically inflamed [SI] horses). Multiple clinical and hematological/biochemical examinations were performed, and serial blood samples were analyzed by reverse transcription quantitative real-time PCR. Post-induction expression profiles of all genes were compared between study groups using principal component analysis (PCA) and hierarchical clustering. Results: Moderate synovitis and mild systemic inflammation of approximately 24 h duration was confirmed by clinical and paraclinical observations in LI and SI horses, respectively. In the LI group, samples obtained 3-16 h post-injection showed distinct clustering in the PCA compared with baseline levels, indicating a transcriptional response to local inflammation in PBLs in this time interval. There was no clinical or hematological indication of actual systemic inflammation. There was a clear separation of all LI samples from all SI samples in two distinct clusters, indicating that expression profiles in the two study groups were different, independent of time since LPS injection. Co-regulated genes formed four clusters across study groups which were distinctly differently regulated. Only few of individual genes displayed different expression between the study groups at all times after LPS injection. Conclusions: Local inflammation in horses initiated an innate transcriptional response in PBLs, which differed from the transcriptional response during the early phase of systemic inflammation. This study may provide new insights into the immunobiology of PBLs during the transition of local inflammation into a systemic state.
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Publication Date: 2016-06-01 PubMed ID: 27250718PubMed Central: PMC4888743DOI: 10.1186/s12917-016-0706-8Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study explores how local inflammation in horses can potentially evolve into a broader, systemic inflammation by analyzing the immune response of peripheral blood leukocytes (PBLs) to local inflammation. Moreover, the study also compares this response with the immune response during early acute systemic inflammation. Several clinical, hematological, and biochemical tests were conducted, along with analyzing gene expressions.

Study Methodology

  • The study used a cross-over model comprising six horses which were exposed to lipopolysaccharide (LPS), a type of bacterial endotoxin, to induce acute synovitis (local inflammation) and endotoxemia (systemic inflammation).
  • The horses were divided into two groups – those with local inflammation (LI) experienced LPS-induced acute synovitis following intraarticular LPS injection, while the systemically inflamed (SI) group underwent endotoxemia after intravenous LPS injection.
  • Expression responses of 22 inflammation-related genes were traced and measured in the leukocytes of the horses’ blood.
  • Serial blood samples were acquired for analysis using reverse transcription quantitative real-time PCR, which is a technique used for detecting and measuring nucleic acids.
  • A Principal Component Analysis (PCA) and hierarchical clustering were used to compare post-induction gene expression profiles between the study groups.

Study Findings

  • Observations confirmed that there was moderate synovitis and mild systemic inflammation of about 24 hours duration in LI and SI horses respectively.
  • For the LI group, samples taken 3-16 hours post LPS injection displayed clear clustering in the PCA as compared to baseline levels, indicating a transcriptional response to local inflammation in PBLs within this time frame.
  • Notably, there was no sign of actual systemic inflammation either clinically or hematologically.
  • There was a clear separation of all LI samples from all SI samples into two distinct clusters, indicating that the gene expression profiles in the two study groups were different regardless of the time lapsed since LPS injection.
  • Co-regulated genes formed four different clusters which were distinctly regulated across study groups.
  • However, only a few individual genes exhibited different expressions between the study groups at all times following LPS injection.

Conclusion

  • The results indicate that local inflammation activates an innate transcriptional response in PBLs, which differs from the transcriptional response during the initial phase of systemic inflammation.
  • This investigation provides new insights into the immunobiology of PBLs during the transition of local inflammation to a systemic state in horses and can potentially shed light on similar processes in other mammals.

Cite This Article

APA
Vinther AM, Heegaard PM, Skovgaard K, Buhl R, Andreassen SM, Andersen PH. (2016). Characterization and differentiation of equine experimental local and early systemic inflammation by expression responses of inflammation-related genes in peripheral blood leukocytes. BMC Vet Res, 12, 83. https://doi.org/10.1186/s12917-016-0706-8

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 12
Pages: 83
PII: 83

Researcher Affiliations

Vinther, Anne Mette L
  • Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark. aml.vinther@gmail.com.
Heegaard, Peter M H
  • Innate Immunology Group, Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
Skovgaard, Kerstin
  • Innate Immunology Group, Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark, Frederiksberg, Denmark.
Buhl, Rikke
  • Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Andreassen, Stine M
  • Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Taastrup, Denmark.
Andersen, Pia H
  • Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.

MeSH Terms

  • Animals
  • Cross-Over Studies
  • Female
  • Gene Expression Profiling
  • Horses
  • Immunity, Innate
  • Inflammation / genetics
  • Inflammation / veterinary
  • Inflammation Mediators / metabolism
  • Leukocytes / immunology
  • Lipopolysaccharides
  • Male
  • Synovitis / chemically induced
  • Synovitis / immunology
  • Synovitis / veterinary

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