Immunomodulatory effects of interferon-beta-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 pa tients with RR-MS without immunomodulatory therapy, the expression of TGF b eta -1-mRNA by peripheral blood mononuclear cells (PBMC) was persistently i ncreased at week 6, month 3 and month 6 (p less than or equal to 0.05), tha t 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 w ere 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 aft er stimulation with IFN beta -1b for 24 h in vitro. Serum levels of soluble vascular cell adhesion molecule (sVCAM) were increased during the whole ti me of in vivo treatment (p < 0.01). The CD8CD38 lymphocyte subpopulation wa s continuously elevated from day 5 up to month 6 (p < 0.01) in the MS patie nts treated with IFN beta -1b in vivo. No persistent, significant changes w ere demonstrable concerning the percentage of total CD4, CD8, CD19 nor in C D4 subpopulations (CD4CD29, CD4CD45RA). The present data suggest that IFN b eta -1b induces the mRNA expression of TGF beta -1 and TGF beta -R-II by PB MC, decreases that of TNF alpha and increases levels of sVCAM-1 and of circ ulating activated CD8 cells (CD8CD38) in blood. These might be other mechan isms by which IFN beta -1b mediates its positive effects in the treatment o f MS patients. (C) 2001 Elsevier Science B.V. All rights reserved.