Immunomodulatory effects of interferon-beta-1b in vivo: induction of the expression of transforming growth factor-beta1 and its receptor type II.
The mechanisms by which interferon-beta-1b (IFNbeta-1b) acts in the treatment of patients with multiple sclerosis (MS) are not completely known. A total of 10 MS patients were treated with 8 million units of IFNbeta-1b every other day. Compared to baseline and control group the expression of TGFbeta-1-mRNA by PBMC was persistently increased at week 6, month 3 and month 6 (p < or = 0.04), that of the TGFbeta-1 receptor type II from day 5 up to month 6 (p < 0.01). The mRNA and protein expression of tumor necrosis factor-alpha (TNFalpha)-receptor (55 kDa) was only temporarily elevated at the beginning of the therapy. Serum levels of sVCAM were increased during the whole time of treatment (p < 0.01). The CD8CD38 lymphocyte subpopulation was continuously elevated from day 5 up to month 6 (p < 0.01). No persistently significant changes were demonstrable concerning the percentage of total CD4, CD8, CD19 or in CD4 subpopulations (CD4CD29, CD4CD45RA). The present data suggest that IFNbeta-1b induces the expression of TGFbeta-1- and TGFbeta-R-II-mRNA by PBMC and increases levels of sVCAM-1 and of circulating activated CD8 cells (CD8CD38) in serum. These might be other mechanisms by which IFNbeta-1b mediates its positive effects in the treatment of MS patients.
Ossege
L M
LM
Institute of Neurology, Ruhr-University of Bochum, BG Klinikum Bergmannsheil, Germany.
Sindern
E
E
Patzold
T
T
Malin
J P
JP
D000328:Adult; D018941:Antigens, CD19 / Q000032:analysis / Q000276:immunology; D001402:B-Lymphocytes / Q000737:chemistry / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D018076:DNA, Complementary; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D016899:Interferon-beta / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D009103:Multiple Sclerosis / Q000276:immunology; D015213:Neuroimmunomodulation / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology
D018941:Antigens, CD19; D018076:DNA, Complementary; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D018124:Receptors, Tumor Necrosis Factor; D016212:Transforming Growth Factor beta; D019010:Vascular Cell Adhesion Molecule-1; D016899:Interferon-beta; D017493:Leukocyte Common Antigens