INGESTED IFN-ALPHA HAS BIOLOGICAL EFFECTS IN HUMANS WITH RELAPSING-REMITTING MULTIPLE-SCLEROSIS

Parenterally administered human recombinant type I interferons (hrIFN) in relapsing-remitting multiple sclerosis (RRMS) decrease relapses an d spontaneous in vitro IFN-gamma production, reduce clinical Progressi on, and decrease magnetic resonance imaging (MRI)-defined disease acti vity and lesions. Parenterally administered type I IFN use is limited by clinical and chemical toxicities, and the induction of antibodies t hat abrogate their activity in vivo correlated with the loss of clinic al benefit Therefore, we determined whether ingested IFN-alpha was non -toxic and had biological effects in humans. Ingested hrIFN-alpha show ed no toxicity in normal volunteers or patients with RRMS at doses ran ging from 300 to 100 000 units. In subjects with RRMS, a significant d ecrease in Con A-mediated proliferation and serum soluble intercellula r adhesion molecule-1 (sICAM-1), a surrogate measure for disease activ ity in MS, was found after ingesting 10 000 and 30 000 units IFN-alpha The RRMS subjects also showed decreased IL-2 secretion after ingestin g 10 000 units IFN-alpha, and decreased IFN-gamma, TGF-beta and IL-10 production after ingesting 30 000 units IFN-alpha. The decreased secre tion of IFN-gamma and IL-2 by ingested IFN-alpha suggests that oral IF N-alpha may cause a functional inhibition of Th I-like T helper cells in RRMS, a potential site of intervention at the level of effector T c ells in MS. Our studies support the oral use of human IFN-alpha as a b iological response modifier in humans.