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Effects of intravenous methylprednisolone therapy on leukocyte and soluble adhesion molecule expression in MS
A G Droogan1, A D Crockard, S A McMillan
1Department of Neurology, Royal Hospitals Trust, Belfast, Northern Ireland.
Abstract:
Intravenous methylprednisolone (IVMP) may inhibit inflammatory cell recruitment to active MS lesions by effects on leukocyte or endothelial cell adhesion molecule expression. We investigated 15 MS patients in relapse receiving a 5-day course of IVMP (500 mg/day) and 15 normal subjects. Patients' blood samples were obtained pretreatment, at 6 and 24 hours after the first dose, and 48 hours after completion of therapy. Levels of L-selectin, leukocyte functional antigen 1 (LFA-1), Mac-1, and very late activation antigen 4 (VLA-4) expression were determined on alphabeta and gammadelta T cells and monocytes by dual-color immunofluorescent flow cytometry. Serum levels of soluble (s) L-selectin, sE-selectin, soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured by ELISA. There was a marked decrease in the T-cell and monocyte counts at 6 hours after therapy, with recovery to baseline at 24 to 48 hours. Adhesion molecule expression was normal on circulating T cells and monocytes in active MS. IVMP resulted in significant changes in the percent adhesion molecule expression on monocytes: increased L-selectin expression at 24 hours, decreased Mac-1 expression at 6 hours, and decreased VLA-4 expression at 6 hours and 24 hours following treatment. T-cell adhesion molecule expression was unaffected by the therapy. Serum sE-selectin was reduced at 6 hours and 24 hours following treatment. IVMP alters the distribution and kinetics of monocyte adhesion molecule expression and endothelial cell release of E-selectin, which may limit monocyte recruitment to areas of tissue destruction in MS.
Insights
Intravenous methylprednisolone (IVMP) treatment for multiple sclerosis (MS) relapse alters monocyte adhesion molecule expression and reduces soluble E-selectin. This may limit inflammatory cell recruitment to MS lesions.
Area of Science:
- Neuroimmunology
- Molecular Immunology
- Clinical Therapeutics
Background:
- Multiple Sclerosis (MS) involves inflammatory cell infiltration into the central nervous system.
- Intravenous methylprednisolone (IVMP) is a common treatment for MS relapses, potentially by modulating inflammatory cell adhesion.
- The precise mechanisms by which IVMP affects adhesion molecule expression in MS remain incompletely understood.
Purpose of the Study:
- To investigate the effects of IVMP on leukocyte and soluble adhesion molecule expression in patients with active MS lesions.
- To determine if IVMP alters the expression of L-selectin, LFA-1, Mac-1, and VLA-4 on T cells and monocytes.
- To assess changes in serum levels of soluble adhesion molecules (sL-selectin, sE-selectin, sICAM-1, sVCAM-1) following IVMP treatment.
Main Methods:
- Studied 15 MS patients in relapse receiving IVMP and 15 healthy controls.
- Collected blood samples pre-treatment, and at 6, 24, and 48 hours post-therapy initiation.
- Quantified adhesion molecule expression on T cells and monocytes using flow cytometry and measured serum soluble adhesion molecules via ELISA.
Main Results:
- IVMP caused a transient decrease in T-cell and monocyte counts.
- Monocyte adhesion molecule expression was significantly altered: increased L-selectin, decreased Mac-1 and VLA-4 post-treatment.
- Serum soluble E-selectin levels were reduced following IVMP, while T-cell adhesion molecule expression remained unchanged.
Conclusions:
- IVMP treatment modifies monocyte adhesion molecule expression kinetics and reduces soluble E-selectin levels.
- These IVMP-induced changes may contribute to limiting monocyte recruitment to active MS lesions.
- The findings provide insights into the immunomodulatory effects of IVMP in MS pathogenesis.