Ingested (oral) IFN-alpha represses TNF-alpha mRNA in relapsing-remitting multiple sclerosis

J Interferon Cytokine Res. 2006 Mar;26(3):150-5. doi: 10.1089/jir.2006.26.150.

Abstract

In a phase II trial in relapsing-remitting multiple sclerosis (RRMS), patients ingesting 10,000 IU, but not 30,000 IU, interferon-alpha (IFN-alpha) showed fewer gadolinium enhancements at months 5 and 6, along with decreased proinflammatory tumor necrosis factor-alpha (TNF-alpha) protein secretion. Therefore, we examined MxA mRNA induction and TNF-alpha mRNA repression after 100, 300, 1,000, 3,000, and 10,000 IU doses of ingested IFN-alpha in 24 RRMS patients to determine the optimal dose for future clinical trials in MS. Maximal TNF-alpha repression occurs at 100, 1,000, and 3,000 IU. These data provide new optimal doses for additional clinical studies using ingested IFN-alpha in MS.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Dose-Response Relationship, Drug
  • GTP-Binding Proteins / analysis
  • GTP-Binding Proteins / metabolism
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / therapeutic use*
  • Leukocytes, Mononuclear / drug effects
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology*
  • Myxovirus Resistance Proteins
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Interferon-alpha
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • GTP-Binding Proteins