Anti-inflammatory drugs decrease infection of brain endothelial cells with EHV-1 in vitro
S. Goehring, K. Brandes, L. V. Ashton, L. A. Wittenburg, F. J. Olea-Popelka, D. P. Lunn and G. Soboll Hussey
This in vitro study set out to determine the effects of several anti-inflammatory drugs on endothelial cells infected with equine herpesvirus-1 (EHV-1). The drugs tested were acetylsalicylic acid, lidocaine hydrochloride 2%, firocoxib, flunixin meglumine and dexamethasone sodium disphosphate at therapeutic concentrations. Peripheral blood mononuclear cells (PBMC) were infected with EHV-1, and three experiments were performed.
Experiment 1 used immortalised equine carotid artery cells. The degree of infection and subsequent cell lysis was detectable as a ‘plaque’, allowing cell infection to be measured by ‘plaque count per well’. All five anti-inflammatory drugs resulted in significantly decreased plaque counts compared to non-treated monolayers. Experiment 2 used brain-derived endothelial cells and significant reduction in plaque counts were observed in monolayers treated with lidocaine, firocoxib and dexamethasone. Experiment 3 evaluated the effect of the drugs over a restricted 24-hour period on infected PBMC alone, brain endothelial cells alone or both together. Lidocaine and firocoxib significantly reduced plaque counts when both types of cells were incubated together. This effect was not seen when only one cell type was infected, with the exception of dexamethasone, which significantly decreased plaque counts in PBMC cells.
These results provide further evidence that infection of the central nervous system with EHV-1 appears to occur by contact between infected PBMC and endothelial cells. Crucially, infection of endothelial cells in vitro is reduced by incubation with anti-inflammatory drugs, including commonly used NSAIDs. More research is warranted to determine whether anti-inflammatories result in reduced infection rates in clinical cases of disease.
Pro-active use of anti-inflammatories in the early stage of EHV-1 neurological disease may be beneficial, with more research needed in this area.