Effects of intravenous methylprednisolone therapy on leukocyte and soluble adhesion molecule expression in MS.
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.
Droogan
A G
AG
Department of Neurology, Royal Hospitals Trust, Belfast, Northern Ireland.
Crockard
A D
AD
McMillan
S A
SA
Hawkins
S A
SA
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015415:Biomarkers; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism*; D019040:E-Selectin / Q000032:analysis / Q000097:blood; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000097:blood; D019041:L-Selectin / Q000032:analysis / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D012995:Solubility; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis / Q000097:blood
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D008775:Methylprednisolone