title: Ingested type I interferon: state of the art as treatment for autoimmunity.
abstract: 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-alpha preserved residual beta-cell function in recent onset patients. In a second phase I trial, treatment of rheumatoid arthritis with ingested IFN-alpha 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-gamma production after ingesting IFN-alpha. In a phase II randomized, placebo-controlled, double-blind trial in multiple sclerosis, 10,000 IU ingested IFN-alpha significantly decreased gadolinium enhancements compared with the placebo group at month 5. Tumor necrosis factor-alpha and IFN-gamma cytokine secretion in the 10,000 IU group at month 5 showed a significant decrease that corresponded with the effect of ingested IFN-alpha on decreasing gadolinium enhancements. Ingested IFN-alpha was not toxic in any of these clinical trials. These studies suggest that ingested IFN-alpha may have a potential role in the treatment of autoimmunity.
authors.affiliation: Multiple Sclerosis Research Group, Department of Neurology, Graduate School of Biomedical Sciences in Immunology, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. stanley.a.brod@uth.tmc.edu
authors.forename: Staley A
authors.initials: SA
authors.lastname: Brod
mesh_terms: D000284:Administration, Oral; D001327:Autoimmune Diseases / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D007370:Interferon Type I