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

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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 (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.
Funding Information
  • Deutsche Forschungsgemeinschaft (Wa 1343/1-1)
  • Mildred Scheel Stiftung
  • NIH

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