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Methylprednisolone reduces adhesion molecules in blood and cerebrospinal fluid in patients with MS
1Department of Neurology, Tampere University Hospital, Finland.
Objective:
To analyze the expression of adhesion molecules on mononuclear cells from blood and CSF of patients with exacerbations of MS before and after megadose IV methylprednisolone (MP).
Background:
Adhesion molecules regulate transmigration of lymphocytes and monocytes/macrophages to the CNS and have an important role in the pathogenesis of MS.
Methods:
The expression of very late activation antigen 4 (VLA-4) and vascular cell adhesion molecule 1, lymphocyte function-associated antigen 1 (LFA-1), and intercellular adhesion molecule 1 (ICAM-1) was analyzed immunocytologically on lymphocytes and monocytes from blood and CSF of 23 patients and 11 healthy control subjects. The results were correlated with the Expanded Disability Status Scale and in half of the patients with the number of T2-weighted MS plaques and brain atrophy analyzed by MRI.
Results:
After treatment, the mean proportions of VLA-4, LFA-1, and ICAM-1 on blood lymphocytes (p < 0.0003, p < 0.00001, p < 0.01) and monocytes (p < 0.0001, p < 0.0002, p < 0.007) of 23 patients decreased. The expression of these adhesion proteins was also diminished on CSF leukocytes. However, even after treatment, the levels of VLA-4 and LFA-1 on lymphocytes from blood of MS patients remained higher than in the control subjects. The level of VLA-4 and LFA-1 on blood lymphocytes (r=0.67, p=0.023) and VLA-4 on monocytes (r=0.61, p=0.047) correlated with the number of T2-weighted lesions.
Conclusions:
Megadose MP may suppress brain inflammation by reducing the expression of adhesion molecules on mononuclear cells from blood and CSF of MS patients. The inhibition of cellular trafficking in MS by MP offers an important means of altering the autoimmune response in MS.
Insights
High-dose methylprednisolone (MP) treatment reduced key adhesion molecules on immune cells in multiple sclerosis (MS) patients. This suggests MP may suppress neuroinflammation by limiting immune cell entry into the central nervous system (CNS).
Area of Science:
- Neuroimmunology
- Cellular Biology
- Neurology
Background:
- Adhesion molecules are crucial for immune cell trafficking to the central nervous system (CNS), playing a significant role in multiple sclerosis (MS) pathogenesis.
- Understanding the modulation of these molecules is key to developing targeted therapies for MS.
Purpose of the Study:
- To investigate the expression of specific adhesion molecules on mononuclear cells in the blood and cerebrospinal fluid (CSF) of MS patients during exacerbations.
- To evaluate the effect of high-dose intravenous methylprednisolone (MP) on the expression of these adhesion molecules.
Main Methods:
- Immunocytological analysis of very late activation antigen 4 (VLA-4), lymphocyte function-associated antigen 1 (LFA-1), and intercellular adhesion molecule 1 (ICAM-1) on lymphocytes and monocytes.
- Samples were collected from 23 MS patients before and after MP treatment, and from 11 healthy controls.
- Correlation of adhesion molecule expression with clinical disability (Expanded Disability Status Scale) and MRI-based measures of MS lesions and brain atrophy.
Main Results:
- MP treatment significantly decreased the expression of VLA-4, LFA-1, and ICAM-1 on both blood lymphocytes and monocytes in MS patients.
- A reduction in these adhesion molecules was also observed on CSF leukocytes following MP treatment.
- Despite treatment, VLA-4 and LFA-1 levels on blood lymphocytes remained higher in MS patients compared to controls, and correlated with lesion load.
Conclusions:
- High-dose MP therapy may reduce neuroinflammation in MS by downregulating adhesion molecule expression on mononuclear cells.
- MP's ability to inhibit immune cell trafficking offers a potential mechanism for modulating the autoimmune response in MS.