Oral Use of Interferon

Abstract

Interferon-alpha (IFN-alpha) given orally has biological activity in humans and other animals. The dose providing the most benefit delivers IFN-alpha to the oral mucosa in a concentration (10(2)-10(3) IU), similar to that naturally produced in the nasal secretions during respiratory infections. In contrast, conventional IFN therapy employs parenteral doses of > 10(6) IU and, for this reason, orally administered IFN therapies have been called low-dose treatments. Efficacy in both animal disease models and human studies has been reported, and the mechanisms whereby oral administration has a systemic effect are under active study in a number of laboratories.

Treatment of primary sjögren's syndrome with low‐dose human interferon alfa administered by the oromucosal route: Combined phase III results

“…Patients returned for oral (weeks 6,12,18,24) and physical (week 24) examinations, measurements of vital signs (weeks 6, 12, 18, 24), reviews of medical history, concomitant medications and adverse events (weeks 6, 12, 18, 24), hematology and blood chemistry tests (weeks 6, 24), and urinalysis (week 24). The safety variables assessed were divided into 7 main categories: 1) hematologic variables of red blood cells, hemoglobin, hematocrit, platelets, white blood cells, segmented neutrophils, lymphocytes, monocytes, eosinophils, and basophils; 2) body weight; 3) vital signs of temperature, heart rate, and blood pressure; 4) blood chemistry variables of glucose, sodium, potassium, chloride, blood urea nitrogen, creatinine, uric acid, phosphorus, calcium, cholesterol, triglycerides, protein, albumin, globulin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transaminase, total bilirubin, and lactate dehydrogenase; 5) adverse events as reported by each subject; 6) urinalysis variables of pH, specific gravity, ketones, protein, glucose, bilirubin, blood, leukocytes, red blood cell count, and microscopic examination of urine; and 7) oral pathoses including fungal infections and episodes of salivary gland enlargement.…”

“…Interferon (IFN) has been shown to enhance phagocytic antigen processing and immune regulatory activity of macrophages (15), specific cytotoxicity of lymphocytes for target cells, and natural killer cell activity (17). The biologic activity of IFN alfa given in low doses via the oromucosal route has been examined in many species, including humans (18). Data from these studies suggest that IFN alfa can trigger a systemic biologic response when administered via the oral mucosa.…”

Heterologous expression of synthetic chicken IFN-γ in transgenic tobacco plants

“…In vivo, IFN-γ exhibited a similar effect (Cummins et al 1999). This interferon-cellular interaction is translated into systemic effects by amplification phenomena secondary to this interaction (Cummins et al 2005).…”

“…The best available data to date suggest that beneficial effects of orally administered IFN-α are mediated by local interactions between the administered IFN-α and certain populations of regulatory cells present in the oropharyngeal mucosa (Cummins et al 1999(Cummins et al , 2005. In vivo, IFN-γ exhibited a similar effect (Cummins et al 1999).…”

“…IFN given orally has biological activity in humans and other animals (Marcus et al 1999;Lowenthal et al 2000;Cummins et al 1999Cummins et al , 2005. The objective of this study was to introduce and express the ChIFN-γ gene in transgenic tobacco using Agrobacterium-mediated transformation.…”