title: Effects of intravenous methylprednisolone therapy on leukocyte and soluble adhesion molecule expression in MS.
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.
authors.affiliation: Department of Neurology, Royal Hospitals Trust, Belfast, Northern Ireland.
authors.forename: A G
authors.initials: AG
authors.lastname: Droogan
authors.forename: A D
authors.initials: AD
authors.lastname: Crockard
authors.forename: S A
authors.initials: SA
authors.lastname: McMillan
authors.forename: S A
authors.initials: SA
authors.lastname: Hawkins
mesh_terms: 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
chemical_list: 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