Ingested type I interferon: a potential treatment for autoimmunity.
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 (MS). 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 (RA) with ingested IFN-alpha reduced the secretion of interleukin-1 (IL-1), a proinflammatory cytokine. In a third phase I trial in MS, there was a significant decrease in peripheral blood mononuclear cell (PBMC) IL-2 and IFN-gamma production after ingesting IFN-alpha. In a phase II randomized, placebo-controlled, double-blind trial in MS, 10,000 IU ingested IFN-alpha significantly decreased gadolinium enhancements compared with the placebo group at month 5. Tumor necrosis factor-alpha (TNF-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.
Brod
Staley A
SA
Multiple Sclerosis Research Group, Department of Neurology, Graduate School of Biomedical Sciences in Immunology, University of Texas Health Science Center at Houston, Houston, TX 77030, USA. staley.a.brod@uth.tmc.edu
D000284:Administration, Oral; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000188:drug therapy*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy
D016898:Interferon-alpha