Methylprednisolone reduces adhesion molecules in blood and cerebrospinal fluid in patients with MS.
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.
Elovaara
I
I
Department of Neurology, Tampere University Hospital, Finland.
Lällä
M
M
Spåre
E
E
Lehtimäki
T
T
Dastidar
P
P
D000328:Adult; D018926:Anti-Allergic Agents / Q000032:analysis; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D005260:Female; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D016169:Lymphocyte Function-Associated Antigen-1 / Q000032:analysis; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000378:metabolism; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D016201:Receptors, Lymphocyte Homing / Q000032:analysis
D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D018799:Intercellular Adhesion Molecule-1; D008775:Methylprednisolone