Ingested IFN-alpha has biological effects in humans with relapsing-remitting multiple sclerosis

Area of Science:

• Immunology
• Neuroimmunology
• Pharmacology

Background:

• Parenteral type I interferons (IFN) are used for relapsing-remitting multiple sclerosis (RRMS) but have toxicities and can induce neutralizing antibodies.
• Limited efficacy and toxicity restrict parenteral IFN use in MS management.

Purpose of the Study:

• To assess the safety and biological activity of orally ingested human recombinant type I interferon-alpha (hrIFN-alpha) in humans.
• To explore oral IFN-alpha as a potential alternative to parenteral administration for MS treatment.

Main Methods:

• A dose-escalation safety and tolerability study of ingested hrIFN-alpha in healthy volunteers and RRMS patients.
• Evaluation of immunological markers, including T-cell proliferation, cytokine production (IFN-gamma, IL-2, TGF-beta, IL-10), and soluble intercellular adhesion molecule-1 (sICAM-1), in RRMS patients post-ingestion.

Main Results:

• Ingested hrIFN-alpha was non-toxic across a wide dosage range (300–100,000 units) in both healthy volunteers and RRMS patients.
• Significant reductions in Con A-mediated T-cell proliferation and serum sICAM-1 levels were observed in RRMS patients after ingesting 10,000 and 30,000 units of IFN-alpha.
• Decreased secretion of IL-2, IFN-gamma, TGF-beta, and IL-10 was noted in RRMS subjects, suggesting a potential modulation of T-helper cell function.

Conclusions:

• Oral administration of hrIFN-alpha is safe and well-tolerated in humans.
• Ingested IFN-alpha exhibits biological activity, including the suppression of immune responses relevant to MS pathogenesis.
• Oral IFN-alpha represents a promising, non-toxic biological response modifier for managing RRMS.