Methylprednisolone Acts on Peripheral Blood Mononuclear Cells and Endothelium in Inhibiting Migration Phenomena in Patients With Multiple Sclerosis
Maurizio Gelati, BS;
Elena Corsini, BS;
Marco De Rossi, MD;
Laura Masini, BS;
Gaetano Bernardi, MD;
Giorgio Massa, MD;
Amerigo Boiardi, MD;
Andrea Salmaggi, MD
Arch Neurol. 2002;59:774-780.
Background Intravenous methylprednisolone hemisuccinate is administered to patients
with multiple sclerosis (MS) during exacerbations to improve the rate of recovery.
Corticosteroids could be beneficial in MS exacerbations also by decreasing
transmigration of peripheral blood mononuclear cells (PBMNCs) through the
blood-brain barrier.
Objectives To evaluate how in vivo intravenous methylprednisolone treatment in
patients with MS could influence transmigration of PBMNCs in an in vitro model;
to perform transmigration experiments through a methylprednisolone-treated
endothelium with PBMNCs from untreated healthy control subjects to evaluate
putative selective effects of corticosteroids on endothelium; concomitantly,
to quantify the concentration of matrix metalloproteinases 2 and 9 in supernatants
of PBMNCs and in serum samples from methylprednisolone-treated patients with
MS; to evaluate monokine induced by interferon- release in the supernatants
of human umbilical vein endothelial cells treated with interferon-
alone or interferon- and methylprednisolone; and to perform gene expression
studies of matrix metalloproteinases 2 and 9 in human umbilical vein endothelial
cells and PBMNCs from methylprednisolone-treated patients with MS.
Patients Eight patients with MS in exacerbation were studied before and 3 and
24 hours after intravenous methylprednisolone treatment, 1 g.
Results The absolute number of transmigrated PBMNCs from methylprednisolone-treated
patients with MS significantly (P<.01) decreased at 3 hours
and increased again at 24 hours, reaching values higher than those before
treatment onset. Methylprednisolone was also able to significantly (P<.03) reduce the number of PBMNCs from healthy controls migrating
through interferon-–stimulated or unstimulated endothelium. In
vitro methylprednisolone treatment decreased monokine induced by interferon-
production in human umbilical vein endothelial cells.
Conclusions Methylprednisolone may be able to decrease transmigration of PBMNCs
through the blood-brain barrier, exerting its inhibitory effects on PBMNCs
and endothelium. A "rebound" of transmigration at 24 hours suggests that a
single infusion is not optimal for achieving a persistent reduction in transmigration.
From the Istituto Nazionale Neurologico "C. Besta," Milan, Italy.
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