Anti-inflammatory drugs decrease infection of brain endothelial cells with EHV-1 in vitro

L. S. Goehring, K. Brandes, L. V. Ashton, Luke Anthony Wittenburg, F. J. Olea-Popelka, D. P. Lunn, G. Soboll Hussey

Research output: Contribution to journalArticle

Abstract

Background: Equine herpesvirus-associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus-1 (EHV-1) during cell-associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection. Objectives: Evaluating the role of anti-inflammatory drugs in decreasing endothelial cell infection with EHV-1. Study design: In vitro assay, crossover design, multiple drug testing. Methods: In vitro modified infectious centre assay using immortalised carotid artery endothelial cells or primary brain endothelial cells with plaque counts per well as outcome. Cells were either anti-inflammatory drug treated or left untreated. Results: Significant reduction of plaque count when cells were treated compared with untreated cells. No dose-dependent effect when drug concentrations were increased to 10× dose. Treatment of both peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) is required for significant plaque count reduction. Main limitations: In vitro study. Conclusions: Anti-inflammatory drugs decrease infection of endothelial cells likely by reducing contact between EHV-1 infected PBMC and endothelial cells in vitro. The role of adhesion molecules in this process needs further investigation. In vitro results suggest anti-inflammatory drug therapy during EHV-1 infection and viraemia in horses could be clinically relevant.

Original languageEnglish (US)
JournalEquine Veterinary Journal
DOIs
StateAccepted/In press - 2017
Externally publishedYes

Fingerprint

Equid Herpesvirus 1
anti-inflammatory agents
Equid herpesvirus 1
endothelial cells
Anti-Inflammatory Agents
Endothelial Cells
brain
Brain
Infection
infection
Pharmaceutical Preparations
Viremia
viremia
mononuclear leukocytes
Blood Cells
Horses
cells
adhesion
myeloencephalopathy
In Vitro Techniques

Keywords

  • Dexamethasone
  • EHM
  • Firocoxib
  • Horse
  • Lidocaine

ASJC Scopus subject areas

  • Equine

Cite this

Goehring, L. S., Brandes, K., Ashton, L. V., Wittenburg, L. A., Olea-Popelka, F. J., Lunn, D. P., & Soboll Hussey, G. (Accepted/In press). Anti-inflammatory drugs decrease infection of brain endothelial cells with EHV-1 in vitro. Equine Veterinary Journal. https://doi.org/10.1111/evj.12656

Anti-inflammatory drugs decrease infection of brain endothelial cells with EHV-1 in vitro. / Goehring, L. S.; Brandes, K.; Ashton, L. V.; Wittenburg, Luke Anthony; Olea-Popelka, F. J.; Lunn, D. P.; Soboll Hussey, G.

In: Equine Veterinary Journal, 2017.

Research output: Contribution to journalArticle

Goehring, L. S. ; Brandes, K. ; Ashton, L. V. ; Wittenburg, Luke Anthony ; Olea-Popelka, F. J. ; Lunn, D. P. ; Soboll Hussey, G. / Anti-inflammatory drugs decrease infection of brain endothelial cells with EHV-1 in vitro. In: Equine Veterinary Journal. 2017.
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abstract = "Background: Equine herpesvirus-associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus-1 (EHV-1) during cell-associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection. Objectives: Evaluating the role of anti-inflammatory drugs in decreasing endothelial cell infection with EHV-1. Study design: In vitro assay, crossover design, multiple drug testing. Methods: In vitro modified infectious centre assay using immortalised carotid artery endothelial cells or primary brain endothelial cells with plaque counts per well as outcome. Cells were either anti-inflammatory drug treated or left untreated. Results: Significant reduction of plaque count when cells were treated compared with untreated cells. No dose-dependent effect when drug concentrations were increased to 10× dose. Treatment of both peripheral blood mononuclear cells (PBMC) and endothelial cells (EC) is required for significant plaque count reduction. Main limitations: In vitro study. Conclusions: Anti-inflammatory drugs decrease infection of endothelial cells likely by reducing contact between EHV-1 infected PBMC and endothelial cells in vitro. The role of adhesion molecules in this process needs further investigation. In vitro results suggest anti-inflammatory drug therapy during EHV-1 infection and viraemia in horses could be clinically relevant.",
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