Treatment with methylprednisolone in relapses of multiple sclerosis patients: immunological evidence of immediate and short-term but not long-lasting effects

Abstract

Relapses of multiple sclerosis (MS) are treated commonly with high-dose intravenous methylprednisolone (MP) given over a period of 3-5 days. The mechanisms responsible for the beneficial effects of MP in attacks are not clearly established. It is also controversial whether this treatment may have a long-term effect. Here, peripheral blood samples from relapsing--remitting MS patients in acute relapse were analysed by flow cytometry just before steroid treatment and at different time points after initiation of the therapy. We observed an immediate (day 3) decrease in the percentage of CD4+ lymphocytes, with a relative increase in the memory (CD4+CD45R0+) subpopulation. A longer standing effect of MP on IFN-gamma production, CD54, CCR5, CXCR3 and CD95 (Fas) expression was also observed on CD4+ cells after 1 month of treatment initiation. Six months after the therapy, during clinical remission, no changes due to ivMP therapy were detected. These results support that MP treatment of relapses induces immediate post-treatment and short-term effects on the immune system that could partly account for the clinical and radiological improvement observed in MS patients. However, no conclusion can be drawn as to a possible long-term or even intermediate influence of ivMP treatment on the course of the disease.

Fig. 1

ivMP treatment induces a transient decrease in the percentage of CD3⁺ cells. Blood samples of the MS patients (n = 16) were stained with saturating amounts of the surface marker CD3-PE. After 3 days of therapy a transient decrease in the percentage of T lymphocytes (CD3⁺) was observed (P < 0·01) in all patients analysed (n = 16). On day 30 there was a recovery to pre treatment levels (n = 12)

Fig. 2

Modification of adhesion molecule expression on CD4⁺CD45RO⁺ lymphocytes by ivMP. Samples of 16 MS patients were stained with anti-CD4-PerCP plus anti-CD45RO-APC, and different FITC or PE-conjugated MoAb as indicated in the Materials and methods section. The percentage of positive cells (Fig. 2a) and the number of molecules expressed per cell (measured by MFI) were analysed (Fig. 2b). Data are presented as mean ± s.e.m. *P < 0·05; P-values indicate significant differences in relation to t = 0 (relapse). , t = 0; ▪, t = 3; , t = 30; □, t = 180.