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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.