Adhesion molecules in multiple sclerosis - Relation to subtypes of diseasemethylprednisolone therapy

Objectives: To determine levels of adhesion molecules in blood and cerebros pinal fluid (CSF) samples from patients with different subtypes and activit ies of multiple sclerosis (MS) and to assess the effect of intravenous meth ylprednisolone sodium succinate treatment on the levels of soluble adhesion molecules. Design: The expressions of very late activation antigen + (VLA-4). lymphocy te function associated antigen 1 (LFA-1)I vascular cell adhesion molecule I (VCAM-1). and intercellular adhesion molecule 1 (ICAM-1) were determined i mmunocytochemically. and levels of soluble VCAM-1. ICAM-1. and E-selectin, by means of enzyme immunoassay) technique. The volumes of T2- and T1-weight ed MS plaques and brain atrophy were determined by means of the semiautomat ic magnetic resonance imaging (MRI) segmentation technique. Setting: A university hospital in Finland, Patients: One hundred subjects (71 patients with MS and 29 healthy control subjects). The subtypes of MS were relapsing-remitting (RRMS [n = 26]), sec ondary progressive (SPMS [n= 20], and primary progressive (PPMS [n = 25]). Results: In patients with RRMS and SPMS, the expressions of VLA-4 and LFA-1 on immune cells from blood were at least 1.5- to 3-fold higher than in con trols(RRMS, P = .002 and P < .001, respectively,; SPMS, P = .03 and P = .00 1, respectively). In RRMS, LFA-1 and ICAM-1 expression in blood was more up -regulated than in SPMS (P = .03 and P = .01, respectiely). The expressions of adhesion molecules on CSF lymphocytes in RRMS and SPMS were of similar magnitude, but the proportions of CSF VLA-4- and LFA-expressing lymphocytes were 3- to 5-fold higher than in controls (P = .04 and P = .008, respectiv ely), The levels of serum soluble VCAM were higher in SPMS than in RRMS (P = .005) or PPMS (P = .04). Intravenous methylprednisolone treatment of pati ents with RRMS in exacerbation caused a significant reduction in the serum levels of soluble VCAM-1 and E-selectin (P < .001). In SPMS, the volumes of T2-weighted plaques correlated with the serum level of soluble ICAM-1 (r = 0.64; p = .03). Conclusions: Up-regulated adhesion molecules in blood and CSF indicate sust ained potential for inflammation in the CNS throughout the clinical spectru m of MS. Therapies interfering with cell adhesion may be of key importance in suppressing MS.