High-dose methylprednisolone reduces cytokine-induced adhesion molecules on human brain endothelium.
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
gamma-IFN-induced HLA-DR was down-regulated in a dose-dependent manner by MP. High-dose MP reduced the TNF-alpha-induced ICAM-1 and VCAM-1 expression.


CONCLUSIONS
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.
Gelati
M
M
Istituto Nazionale Neurologico C. Besta, Milano, Italy.
Corsini
E
E
Dufour
A
A
Massa
G
G
Giombini
S
S
Solero
C L
CL
Salmaggi
A
A
D000328:Adult; D000368:Aged; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000494:pharmacology; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D005938:Glucocorticoids; D006684:HLA-DR Antigens; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D008775:Methylprednisolone