High-dose methylprednisolone reduces cytokine-induced adhesion molecules on human brain endothelium

Objective: We investigated the in vitro effects of low- and high-dose methy lprednisolone (MP) on the cytokine-induced expression of HLA-DR, ICAM-1 and VCAM-1 on human brain microvessel endothelial cells (HBMECs). Methods: Bra in endothelium was obtained from microvessels included in the apparently no rmal white matter of surgical specimens of nine patients. Cells were staine d with monoclonal antibodies anti-HLA-DR, anti-ICAM-1 and anti-VCAM-1 and a nalysed by flow cytometry as fluorescence histograms. The mean fluorescence intensity (MFI) of HBMECs treated with different stimuli was calculated. R esults: gamma-IFN-induced HLA-DR was down-regulated in a dose-dependent man ner by MP. High-dose MP reduced the TNF-alpha-induced ICAM-1 and VCAM-1 exp ression, Conclusions: The down-regulation of adhesion molecules on cerebral endothelial cells could decrease mononuclear cell transmigration through t he blood brain barrier and consequently the perivascular infiltrates. The r esults add support to the rationale for high-dose MP treatment in multiple sclerosis relapses.