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High-Dose Methylprednisolone Reduces Cytokine-Induced Adhesion Molecules on Human Brain Endothelium

Published online by Cambridge University Press:  02 December 2014

Maurizio Gelati
Affiliation:
Istituto Nazionale Neurologico C.Besta, Milano, Italy.
Elena Corsini
Affiliation:
Istituto Nazionale Neurologico C.Besta, Milano, Italy.
Anna Dufour
Affiliation:
Istituto Nazionale Neurologico C.Besta, Milano, Italy.
Giorgio Massa
Affiliation:
Istituto Nazionale Neurologico C.Besta, Milano, Italy.
Sergio Giombini
Affiliation:
Istituto Nazionale Neurologico C.Besta, Milano, Italy.
Carlo L.Solero
Affiliation:
Istituto Nazionale Neurologico C.Besta, Milano, Italy.
Andrea Salmaggi
Affiliation:
Istituto Nazionale Neurologico C.Besta, Milano, Italy.
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Abstract

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Objective:

We investigated the in vitro effects of low- and high-dose methylprednisolone (MP) on the cytokine-induced expression of HLA-DR, ICAM-1 and VCAM-1 on human brain microvessel endothelial cells (HBMECs).

Methods:

Brain endothelium was obtained from microvessels included in the apparently normal white matter of surgical specimens of nine patients. Cells were stained with monoclonal antibodies anti-HLA-DR, anti-ICAM-1 and anti-VCAM-1 and analysed by flow cytometry as fluorescence histograms. The mean fluorescence intensity (MFI) of HBMECs treated with different stimuli was calculated.

Results:

3-IFN-induced HLA-DR was down-regulated in a dose-dependent manner by MP. High-dose MP reduced the TNF-3-induced ICAM-1 and VCAM-1 expression.

Conclusion:

The down-regulation of adhesion molecules on cerebral endothelial cells could decrease mononuclear cell transmigration through the blood brain barrier and consequently the perivascular infiltrates. The results add support to the rationale for high-dose MP treatment in multiple sclerosis relapses.

Résumé:

RÉSUMÉ:Objectif:

Nous avons éluées effets de faibles et de fortes doses de méylprednisolone (MP) in vitro sur l’expression de HLA-DR, ICAM-1 et VCAM-1, induite par des cytokines, sur les cellules endothéales de microvaisseaux de cerveaux humains (CEMCHs).

Méodes:

De l’endothéum de cerveau a é obtenu de microvaisseaux provenant de substance blanche apparemment normale contenue dans des spémens chirurgicaux provenant de huit patients. Les cellules ont é marqué au moyens d’anticorps monoclonaux anti-HLA-DR, anti-ICAM-1 et anti-VCAM-1 et analysé par cytoméie de flux sous forme d’histogramme de fluorescence. La moyenne d’intensitée la fluorescence des CEMCHs traité au moyen de diffénts stimuli a é calculé

Réltats:

Le HLA-DR induit par -IFN éit rélé la baisse de faç dose déndante par la MP. De fortes doses de MP diminuaient l’expression de ICAM-1 et VCAM-1 induite par TNF-.

Conclusion:

La rélation àa baisse des moléles d’adhéon sur les cellules endothéales cébrales pourrait diminuer la transmigration des cellules mononucléres àravers la barriè héto-encéalique et conséemment les infiltrats pévasculaires. Ces réltats appuient le concept d’administrer de fortes doses de MP dans le traitement de poussé de sclése en plaques.

Type
Original Articles
Copyright
Copyright © The Canadian Journal of Neurological 2000

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