Immunomodulatory effects of interferon-β-1b in patients with multiple sclerosis

The mechanisms by which IFN beta -lb acts in the treatment of patients with multiple sclerosis (MS) are not completely known. Immunomodulatoly effects of IFN beta -1b were investigated in patients with relapsing-remitting (RR) MS in vivo and in vitro. Compared to baseline and controls, defined as patients with RR-MS without immunomodulatory therapy, the expression of TGF beta -1-mRNA by peripheral blood mononuclear cells (PBMC) was persistently increased at week 6, month 3 and month 6 (p less than or equal to 0.05), that of the TGF beta -1 receptor type II from day 5 up to month 6 (p < 0.01). The expression of TNF alpha -mRNA decreased from day 1 to month 3 compared to day 0 and the controls (p < 0.01). The in vitro investigations performed on isolated peripheral blood lymphocytes demonstrated that these effects were dose-dependent. The mRNA and protein expression of TNF alpha -R-I (55kD-receptor) was only temporarily elevated at the beginning of the therapy in vivo. The expression of TNF alpha -R-I-mRNA increased dose-dependently after stimulation with IFN beta -1b for 24 h in vitro. Serum levels of soluble vascular cell adhesion molecule (sVCAM) were increased during the whole time of in vivo treatment (p < 0.01). The CD8CD38 lymphocyte subpopulation was continuously elevated from day 5 up to month 6 (p < 0.01) in the MS patients treated with IFN beta -1b in vivo. No persistent, significant changes were demonstrable concerning the percentage of total CD4, CD8, CD19 nor in CD4 subpopulations (CD4CD29, CD4CD45RA). The present data suggest that IFN beta -1b induces the mRNA expression of TGF beta -1 and TGF beta -R-II by PBMC, decreases that of TNF alpha and increases levels of sVCAM-1 and of circulating activated CD8 cells (CD8CD38) in blood. These might be other mechanisms by which IFN beta -1b mediates its positive effects in the treatment of MS patients. (C) 2001 Elsevier Science B.V. All rights reserved.