Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes

Multiple sclerosis (MS) is considered an autoimmune disease that is mediated by proinflammatory T helper‐1 lymphocytes. The putative mechanism of interferon‐β (IFN‐β), an approved treatment for MS, includes the inhibition of T‐cell proliferation, blocking of blood‐brain‐barrier opening and T‐cell tr...

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Veröffentlicht in:Annals of neurology 2001-09, Vol.50 (3), p.349-357
Hauptverfasser: Wandinger, Klaus-Peter, Stürzebecher, Claus-Steffen, Bielekova, Bibiana, Detore, Greg, Rosenwald, Andreas, Staudt, Louis M., McFarland, Henry F., Martin, Roland
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container_end_page 357
container_issue 3
container_start_page 349
container_title Annals of neurology
container_volume 50
creator Wandinger, Klaus-Peter
Stürzebecher, Claus-Steffen
Bielekova, Bibiana
Detore, Greg
Rosenwald, Andreas
Staudt, Louis M.
McFarland, Henry F.
Martin, Roland
description Multiple sclerosis (MS) is considered an autoimmune disease that is mediated by proinflammatory T helper‐1 lymphocytes. The putative mechanism of interferon‐β (IFN‐β), an approved treatment for MS, includes the inhibition of T‐cell proliferation, blocking of blood‐brain‐barrier opening and T‐cell transmigration into the brain via interference with cell adhesion, and the upregulation of anti‐inflammatory (TH2) cytokines. In the present study, a gene expression analysis of IFN‐β‐treated peripheral blood mononuclear cells by cDNA microarray documents the broad effects of IFN‐β that are not purely anti‐inflammatory. Specifically, we addressed the effect of IFN‐β on T helper‐1 differentiation‐ or lineage markers such as the IL‐12 receptor β2 chain and the chemokine receptor CCR5 that have been implicated in the pathogenesis of MS. Both markers were significantly upregulated in vitro and in vivo under IFN‐β therapy, supporting that this cytokine exerts complex effects on the immune system. The combination of cDNA microarray and quantitative polymerase chain reaction will expand our knowledge of the immunological effects of such pleiotropic agents as IFN‐β, may provide a key to why certain patients fail to respond, and eventually influence our view of the disease pathogenesis.
doi_str_mv 10.1002/ana.1096
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subjects Adjuvants, Immunologic - pharmacology
Adjuvants, Immunologic - therapeutic use
Biological and medical sciences
Biomarkers - blood
Cell Differentiation - genetics
Cell Differentiation - immunology
Cells, Cultured
Humans
Immunomodulators
Interferon-beta - pharmacology
Interferon-beta - therapeutic use
Leukocytes, Mononuclear - immunology
Leukocytes, Mononuclear - metabolism
Medical sciences
Multiple Sclerosis, Relapsing-Remitting - blood
Multiple Sclerosis, Relapsing-Remitting - drug therapy
Oligonucleotide Array Sequence Analysis - methods
Pharmacology. Drug treatments
Receptors, CCR5 - biosynthesis
Receptors, CCR5 - genetics
Receptors, Interleukin - biosynthesis
Receptors, Interleukin - genetics
Receptors, Interleukin-12
RNA, Messenger - biosynthesis
Th1 Cells - cytology
Th1 Cells - immunology
Th1 Cells - metabolism
Up-Regulation - genetics
Up-Regulation - immunology
title Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes
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