We have proposed a unifying hypothesis of the etiopathogenesis of autoimmunity that defines autoimmunity as a type I interferon (IFN) immunodeficiency syndrome. We have examined toxicity and potential efficacy in three phase I (type 1 diabetes, rheumatoid arthritis, multiple sclerosis) and one phase II clinical trials in multiple sclerosis. In a phase I open-label trial in type 1 diabetes, ingested IFN-α preserved residual β-cell function in recent onset patients. In a second phase I trial, treatment of rheumatoid arthritis with ingested IFN-α reduced the secretion of interleukin (IL)-1, a pro-inflammatory cytokine. In a third phase I trial in multiple sclerosis, there was a significant decrease in peripheral blood mononuclear cell IL-2 and IFN-γ production after ingesting IFN-α. In a phase II randomized, placebo-controlled, double-blind trial in multiple sclerosis, 10,000 IU ingested IFN-α significantly decreased gadolinium enhancements compared with the placebo group at month 5. Tumor necrosis factor-α and IFN-γ cytokine secretion in the 10,000 IU group at month 5 showed a significant decrease that corresponded with the effect of ingested IFN-α on decreasing gadolinium enhancements. Ingested IFN-α was not toxic in any of these clinical trials. These studies suggest that ingested IFN-α may have a potential role in the treatment of autoimmunity.
Deficiency in Type I Interferon Signaling Prevents the Early Interferon-Induced Gene Signature in Pancreatic Islets but Not Type 1 Diabetes in NOD Mice