title: Immunomodulatory effects of interferon-beta-1b in patients with multiple sclerosis.
abstract: The mechanisms by which IFN beta-1b acts in the treatment of patients with multiple sclerosis (MS) are not completely known. Immunomodulatory 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 < or = 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 (55 kD-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.
authors.affiliation: Department of Neurology, Ruhr-University of Bochum, BG Kliniken Bergmannsheil, 44789 Bochum, Germany. ludgera.ossege@ruhr-uni-bochum.de
authors.forename: L M
authors.initials: LM
authors.lastname: Ossege
authors.forename: E
authors.initials: E
authors.lastname: Sindern
authors.forename: T
authors.initials: T
authors.lastname: Patzold
authors.forename: J P
authors.initials: JP
authors.lastname: Malin
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017403:In Situ Hybridization; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D012333:RNA, Messenger / Q000096:biosynthesis; D016707:Tissue Fixation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000068576:Interferon beta-1b; D016899:Interferon-beta; D000068556:Interferon beta-1a