Methylprednisolone acts on peripheral blood mononuclear cells and endothelium in inhibiting migration phenomena in patients with multiple sclerosis.
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.


OBJECTIVE
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-gamma release in the supernatants of human umbilical vein endothelial cells treated with interferon-gamma alone or interferon-gamma 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.


METHODS
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-gamma-stimulated or unstimulated endothelium. In vitro methylprednisolone treatment decreased monokine induced by interferon-gamma 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.
Gelati
Maurizio
M
Istituto Nazionale Neurologico C. Besta, Via Celoria 11, 20133 Milan, Italy.
Corsini
Elena
E
De Rossi
Marco
M
Masini
Laura
L
Bernardi
Gaetano
G
Massa
Giorgio
G
Boiardi
Amerigo
A
Salmaggi
Andrea
A
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000235:genetics; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000032:analysis; D014471:Umbilical Veins / Q000166:cytology
D000893:Anti-Inflammatory Agents; C515187:CXCR3 protein, human; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D007371:Interferon-gamma; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008775:Methylprednisolone