Immunomodulatory effects of IFNbeta-1b on the mRNA-expression of TGFbeta-1 and TNFalpha in vitro.
The mechanisms by which IFNbeta-1b acts in the treatment of multiple sclerosis (MS) patients are not completely known. We investigated the influence of IFNbeta-1b on the mRNA-expression of the immunosuppressive cytokine TGFbeta-1 and the proinflammatory mediator TNFalpha in an in vitro model by the method of non-radioactive in situ hybridization. Peripheral blood lymphocytes (PBL) were isolated from eight patients with relapsing remitting form of MS during remission and from six healthy controls. They were stimulated with IFNbeta-1b in different concentrations for 24 h. In both groups a statistically significant dose-dependent increase of TGFbeta-1-mRNA and decrease of TNFalpha-mRNA was demonstrable in the cultured stimulated blood lymphocytes compared to unstimulated cells. Stimulations with lipopolysaccharide (LPS) led to an increase of both cytokine-mRNAs in the lymphocytes. These data suggest specific and dose-dependent effects of IFNbeta-1b and hint at immunomodulatory properties of this drug to regulate the cytokine dysbalance in MS. This might be one mechanism by which IFNbeta-1b mediates its beneficial effects on the course of the disease.
Ossege
L M
LM
Department of Neurology, BG Kliniken Bergmannsheil, Ruhr University of Bochum, Germany.
Sindern
E
E
Voss
B
B
Malin
J P
JP
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta