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

Klaus Peter Wandinger, Claus Steffen Stürzebecher, Bibiana Bielekova, Greg Detore, Andreas Rosenwald, Louis M. Staudt, Henry F. McFarland, Roland Martin

Research output: Contribution to journalArticle

Abstract

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 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 PCR 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 may influence our view of the disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)349-357
Number of pages9
JournalAnnals of Neurology
Volume50
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

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Interferons
Multiple Sclerosis
Up-Regulation
Genes
Oligonucleotide Array Sequence Analysis
Anti-Inflammatory Agents
Interleukin-12 Receptors
Cytokines
T-Lymphocytes
Chemokine Receptors
Helper-Inducer T-Lymphocytes
Blood-Brain Barrier
Cell Adhesion
Autoimmune Diseases
Immune System
Blood Cells
Cell Proliferation
Gene Expression
Polymerase Chain Reaction
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Wandinger, K. P., Stürzebecher, C. S., Bielekova, B., Detore, G., Rosenwald, A., Staudt, L. M., ... Martin, R. (2001). Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes. Annals of Neurology, 50(3), 349-357. https://doi.org/10.1002/ana.1096

Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes. / Wandinger, Klaus Peter; Stürzebecher, Claus Steffen; Bielekova, Bibiana; Detore, Greg; Rosenwald, Andreas; Staudt, Louis M.; McFarland, Henry F.; Martin, Roland.

In: Annals of Neurology, Vol. 50, No. 3, 2001, p. 349-357.

Research output: Contribution to journalArticle

Wandinger, KP, Stürzebecher, CS, Bielekova, B, Detore, G, Rosenwald, A, Staudt, LM, McFarland, HF & Martin, R 2001, 'Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes', Annals of Neurology, vol. 50, no. 3, pp. 349-357. https://doi.org/10.1002/ana.1096
Wandinger, Klaus Peter ; Stürzebecher, Claus Steffen ; Bielekova, Bibiana ; Detore, Greg ; Rosenwald, Andreas ; Staudt, Louis M. ; McFarland, Henry F. ; Martin, Roland. / Complex immunomodulatory effects of interferon-β in multiple sclerosis include the upregulation of T helper 1-associated marker genes. In: Annals of Neurology. 2001 ; Vol. 50, No. 3. pp. 349-357.
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