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Home / Equine Research Bank / PLoS One / Treatment of limb wounds of horses with orf virus IL-10 and ...
PloS one2018; 13(5); e0197223; doi: 10.1371/journal.pone.0197223

Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development.

Abstract: Bandaging of limb wounds in horses leads to formation of exuberant granulation tissue (EGT) that retards healing due to protracted inflammation, aberrant vascularisation and delayed epithelialisation. EGT is not observed if wounds are left undressed or when wounds are on the body. A previous study showed that short-term administration of proteins derived from orf virus dampened inflammation and promoted epithelialisation of open wounds in horses. Here, we investigated the impact of orf virus interleukin-10 and vascular endothelial growth factor-E on the development and resolution of EGT. Excisional wounds were created on the forelimb of four horses, and bandages were maintained until full healing to induce EGT formation. Matching body wounds were created to ensure EGT was limited to the limb, and to differentiate the effects of the viral proteins on normal healing and on EGT formation. Viral proteins or the hydrogel vehicle control were administered topically to site-matched wounds at day 1, with repeat administration at day 8. Wound healing and EGT formation were monitored macroscopically. Wound margin samples were harvested at 2, 7 and 14 days, and at full healing, with histology used to observe epithelialisation, immunofluorescence used to detect inflammatory cells, angiogenesis and cell death, and qPCR to measure expression of genes regulating inflammation and angiogenesis. Limb wounds developed EGT, and exhibited slower healing than body wounds. Viral protein treatment did not accelerate healing at either location nor limit EGT formation in limb wounds. Treatment of limb wounds did however increase epithelialisation and angiogenesis, without dampening inflammatory cell infiltration or gene expression. The healed wounds also had less occlusion and death of blood vessels and fewer epidermal rete ridges following viral protein treatment. These findings indicate that the viral protein treatment does not suppress wound inflammation or EGT formation, but does promote vascular and epidermal repair and EGT resolution.
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Publication Date: 2018-05-15 PubMed ID: 29763436PubMed Central: PMC5953458DOI: 10.1371/journal.pone.0197223Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

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.

The research reveals that treating limb wounds in horses with orf virus interleukin-10 and vascular endothelial growth factor-E increases epithelialisation and angiogenesis, reducing occlusion and death of blood vessels and epidermal rete ridges after healing. Although these proteins don’t prevent exuberant granulation tissue (EGT) formation or dampen inflammation, they speed up the resolution of EGT.

Methodology and Experiment

  • The researchers created excisional wounds on the forelimb of four horses and maintained bandages on these until full healing. This was to provoke exuberant granulation tissue (EGT) formation.
  • They simultaneously created matching wounds on the body to act as a control group, since EGT is not observed on body wounds.
  • Orf virus interleukin-10 and vascular endothelial growth factor-E proteins were topically applied to site-matched wounds at the start and on day 8.
  • EGT development and wound healing were closely observed and recorded.

Results and Findings

  • EGT, which retards healing, was found to develop in the horses’ limb wounds that were kept bandaged while it wasn’t present in the body wounds.
  • The wounds on the horses’ limbs healed slower than those on the body.
  • The use of viral proteins didn’t quicken the healing process or prevent EGT formation. However, these proteins did promote epithelialisation and angiogenesis in the limb wounds.
  • Despite these proteins, inflammatory cell infiltration and gene expression were not dampened in the wounds.
  • Upon full healing, it was observed that the wounds which received the viral protein treatment had fewer vessel occlusions and less cellular death, along with fewer epidermal rete ridges – a beneficial result.

Conclusion

  • The study concludes that the orf virus interleukin-10 and vascular endothelial growth factor-E proteins, despite not being able to prevent EGT formation or control inflammation, promote epidermal repair and vascular health while accelerating EGT resolution.
  • These findings indicate the potential of these proteins as a treatment option for EGT in horses’ limb wounds, contributing to healthier, quicker healing.

Cite This Article

APA
Wise LM, Bodaan CJ, Stuart GS, Real NC, Lateef Z, Mercer AA, Riley CB, Theoret CL. (2018). Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development. PLoS One, 13(5), e0197223. https://doi.org/10.1371/journal.pone.0197223

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 13
Issue: 5
Pages: e0197223

Researcher Affiliations

Wise, Lyn M
  • Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
  • Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Bodaan, Christa J
  • School of Veterinary Science, Massey University, Palmerston North, New Zealand.
Stuart, Gabriella S
  • Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
  • Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Real, Nicola C
  • Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
  • Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Lateef, Zabeen
  • Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
Mercer, Andrew A
  • Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Riley, Christopher B
  • School of Veterinary Science, Massey University, Palmerston North, New Zealand.
Theoret, Christine L
  • School of Veterinary Science, Massey University, Palmerston North, New Zealand.
  • Comparative Tissue Healing Laboratory, Département de Biomedecine Vétérinaire, Université de Montréal, Montréal, Québec, Canada.

MeSH Terms

  • Animals
  • Hindlimb / metabolism
  • Hindlimb / pathology
  • Horses
  • Hydrogels / pharmacology
  • Interleukin-10 / pharmacology
  • Viral Proteins / pharmacology
  • Wound Healing / drug effects
  • Wounds and Injuries / drug therapy
  • Wounds and Injuries / metabolism
  • Wounds and Injuries / pathology

Conflict of Interest Statement

Competing Interests: The authors have no conflicts to declare except LW and AM, who are co-inventors on a patent (US 9314505; Combination Treatments and Compositions for Wound Healing) for the use of orf virus VEGF-E and IL-10 in treatment of skin wounds. If a product is developed, or the patent is licensed, income may be generated for the inventors. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

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