Ingested (oral) IFN-alpha represses TNF-alpha mRNA in relapsing-remitting multiple sclerosis.
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.
Department of Neurology, University of Texas-Houston, Health Science Center (UTHHSC), Houston, TX 77030, USA. staley.a.brod@uth.tmc.edu
Staley A
SA
Brod
Michael
M
Nguyen
Zachary
Z
Hood
Gregory L
GL
Shipley
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology*; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism*
D016898:Interferon-alpha; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019204:GTP-Binding Proteins