Transmigration of blood mononuclear cells to brain through the blood-brain barrier plays a pivotal role in the pathogenesis of multiple sclerosis (MS). It has been suggested that drugs commonly used in the long-term treatment of MS, such as interferon β (IFN- β) or glatiramer acetate (COP-1), are able to modulate transmigration phenomena. Methylprednisolone (MP) is a synthetic steroid commonly used in the treatment of MS relapses. Glucocorticoids and, in particular, MP exert their anti-inflammatory activity through multiple pathways which might also include the prevention of mononuclear cell/endothelium adhesion and/or transmigration. It has been shown in vivo (Mancuso 1995) that dexamethasone affects leukocyte extravasation maybe by decreasing the expression of adhesion molecules on the vascular wall or decreasing synthesis of chemotactic factors such as chemokines or by a direct action on leukocytes; but the effects on endothelium have not been completely investigated. In the present work, we studied the mechanism(s) of action of MP on endothelial cells using an in vitro model of transmigration. Transmigration of peripheral blood mononuclear cells (PBMNCs) from 6 healthy controls through a human umbilical vein endothelial cells (HUVECs) monolayer unstimulated or stimulated with 250 U/ml of IFN-γ was tested after treatment of HUVECs with 2 concentrations of MP (100 or 300 μg/ml), as suggested by the concentrations found in the cerebrospinal fluid of MS patients treated intravenously with MP (Defer, 1995). We found that both concentrations of MP were able to significantly reduce the number of cells transmigrating through IFN-γ-stimulated or unstimulated endothelium. In conclusion, these results suggest that MP can modulate transmigration through HUVEC monolayers, at least partly via a direct action on endothelial cells; this is probably only one aspect of a more complex modulation, as suggested in our previous studies in which the adhesion ability of PBMNCs from MS patients was reduced by in vivo MP treatment (Gelati, 1997). These data add some rationale to the use of MP in MS relapses.
|Issue number||4 SUPPL.|
|Publication status||Published - 2000|
ASJC Scopus subject areas
- Clinical Neurology