Hostname: page-component-745bb68f8f-kw2vx Total loading time: 0 Render date: 2025-01-13T00:41:31.177Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  02 December 2014

Maurizio Gelati ,
Elena Corsini ,
Anna Dufour ,
Giorgio Massa ,
Sergio Giombini ,
Carlo L.Solero  and
Andrea Salmaggi
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.
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
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
Information
Canadian Journal of Neurological Sciences , Volume 27 , Issue 3 , August 2000 , pp. 241 - 244
Copyright
Copyright © The Canadian Journal of Neurological 2000

References

1. Milligan, M, Newcombe, R, Compston, DAS. A double-blind controlled trial of high-dose methylprednisolone in patients with multiple sclerosis. 1. Clinical effects. J Neurol Neurosurg Psychiatry 1987; 50: 511–516.Google Scholar
2. La Mantia, L, Eoli, M, Milanese, C, et al. Double-blind trial of dexamethasone versus methylprednisolone in Multiple Sclerosis acute relapses. Eur Neurol 1994; 34: 199–203.Google Scholar
3. Gelati, M, Corsini, E, Dufour, A, et al. Reduced adhesion of PBMNCs to endothelium in methylprednisolone-treated MS patients: preliminary results. Acta Neurol Scand 1997; 96: 283–292.Google Scholar
4. Droogan, AG, Crockard, AD, McMillan, SA, et al. Effects of intravenous methylprednisolone therapy on leukocyte and soluble adhesion molecule expression in MS. Neurology 1998;50: 224–230.Google Scholar
5. Aziz, KE, Wakefield, D. Modulation of endothelial cell expression of ICAM-1, E-selectin, and VCAM-1 by ß-estradiol, progesterone, and dexamethasone. Cell Immunol 1996; 167: 79–85.Google Scholar
6. Oppenheimer-Marks, N, Davis, LS, Tompkins-Bogue, D, et al. Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T-lymphocytes. J Immunol 1991; 147: 2913–2923.Google Scholar
7. Baron, JL, Madri, JA, Ruddle, NH, et al. Surface expression of a4 integrin by CD4 T cells is required for their entry into brain parenchyma. J Exp Med 1993; 177: 57–68.Google Scholar
8. Archelos, JJ, Jung, S, Maurer, M, et al. Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1. Ann Neurol 1993; 34: 145–154.CrossRefGoogle Scholar
9. Yednock, TA, Cannon, C, Fritz, LC, et al. Prevention of experimental autoimmune encephalomyelitis by antibodies against a4ß1 integrin. Nature 1992; 356: 63–66.CrossRefGoogle Scholar
10. Goodal, CA, Curtis, ASG, Lang, SC. Modulation of adhesion of lymphocytes to murine brain endothelial cells in vitro: relation to class II Major Histocompatibility Complex expression. J Neuroimmunol 1992; 37: 9–22.Google Scholar
11. Huynh, HK, Dorovini-Zis, K. Effects of interferon-? on primary cultures of human brain microvessel endothelial cells. Am J Pathol 1993; 142: 1265–1278.Google Scholar
12. Wong, D, Dorovini-Zis, K. Up-regulation of intercellular molecule adhesion-1 (ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and lipopolysaccharide. J Neuroimmunol 1992; 39: 11–22.Google Scholar
13. Wong, D, Dorovini-Zis, K. Expression of vascular cell adhesion-1 molecule-1 (VCAM-1) by human brain microvessel endothelial cells in primary cultures. Microvasc Res 1995; 49: 325–339.Google Scholar
14. Dufour, A, Corsini, E, Gelati, M, et al. Modulation of ICAM-1, VCAM-1 and HLA-DR by cytokines and steroids on HUVECs and human brain endothelial cells. J Neurol Sci 1998; 157(2):117–121.Google Scholar
15. Youssef, PP, Triantafillou, S, Parker, A, et al. Effects of pulse methylprednisolone on cell adhesion molecules in the synovial membrane in rheumatoid arthritis. Reduced E-selectin and Intercellular Adhesion Molecule-1 expression. Arthritis Rheum 1996; 39(12): 1970–1979.CrossRefGoogle ScholarPubMed
16. Defer, GL, Barré, J, Ledudal, P, et al. Methylprednisolone infusion during acute exacerbation of MS: plasma and CSF concentrations. Eur Neurol 1995; 35: 143–148.CrossRefGoogle ScholarPubMed
17. Cronstein, BN, Kimmel, SC, Levin, RI, et al. A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leucocyte adhesion to endothelial cells and expression of endothelial-leucocyte adhesion molecule-1 and intercellular adhesion molecule-1. Proc Natl Acad Sci USA 1992; 89: 9991–9995.Google Scholar
18. Corsini, E, Gelati, M, Dufour, A, et al. Effects of ß-IFN-1b treatment in MS patients on adhesion between PBMNCs, HUVECs and MS -HBECs: an in vivo and in vitro study. J Neuroimmunol 1997; 79:76–83.CrossRefGoogle ScholarPubMed
19. Lou, J, Gasche, Y, Zheng, L, et al. Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer. Lab Invest 1999; 79 (8): 1015–1025.Google ScholarPubMed
20. Gasperini, C, Pozzilli, C, Bastianello, S, et al. Effect of steroids on Gd-enhancing lesions before and during recombinant beta interferon 1a treatment in relapsing-remitting multiple sclerosis. Neurology 1998; 50(2): 403–406.Google Scholar
21. Corsini, E, Gelati, M, Dufour, A, et al. Reduction of transendothelial migration of mononuclear cells in ß-IFN 1b treated MS patients. Ann Neurol 1999; 46(3): 435.Google Scholar
22. Rosenberg, GA, Dencoff, JE, Correa, N, et al. Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to bloodbrain barrier injury. Neurology 1996; 46: 1626–1632.Google Scholar