Oromucosal Administration of Interferon to Humans

Abstract

The prevailing dogma is that, to be systemically effective, interferon-alpha (IFNα) must be administered in sufficiently high doses to yield functional blood concentrations. Such an approach to IFNα therapy has proven effective in some instances, but high-dose parenteral IFNα therapy has the disadvantage of causing significant adverse events. Mounting evidence suggests that IFNα delivered into the oral cavity in low doses interacts with the oral mucosa in a unique manner to induce systemic host defense mechanisms without IFNα actually entering the circulation, thus reducing the potential for toxic side effects. A better understanding of the applications and potential benefits of this treatment modality are under active investigation. This paper provides a review of the relevant literature on the clinical use of the oromucosal route of administration of interferon, with an emphasis on the treatment of influenza.

Evidence for Cross-Protection Against Subsequent Febrile Respiratory Illness Episodes From Prior Infections by Different Viruses Among Singapore Military Recruits 2009–2014

“…This again supports a cytokine-mediated antiviral effect. Finding a means to induce such cross-protection without severe side effects could potentially lead to interventions that may be particularly useful in the context of exposure to dangerous viruses for which there is no specific vaccine or antiviral agent [27].…”

Innate endogenous adjuvants prime to desirable immune responses via mucosal routes

“…Type I interferons (IFNs) have been considered as antiviral agents and primed the development of immune responses (Bracci et al, 2008 ). Several clinical reports clearly exhibits mucosal delivery of human IFN-α has direct prophylactic and therapeutic effects on cancers, autoimmune diseases and infections caused by influenza virus, RSV, measles virus, papillomavirus, HIV and hepatitis virus (Beilharz et al, 2010 ). Genes encoding chemokines, cytokines and proteases were significantly up-regulated with mucosal administration of type I IFNs, which are closely associated with antigen processing and lymphocyte activation, migration, apoptosis and protein degradation (Tovey, 2002 ; Namangala et al, 2006 ; Tovey et al, 2008 ).…”

“…The treatment of IFN-α/β increased the antigen-uptake rate of resident APCs in nasal mucus layer of mice (Bracci et al, 2005 ). Mucosal administration of IFN-α in low dose efficaciously activated the proliferation of natural killer cells, B cells and T-cell subpopulations in the peripheral circulation (Beilharz et al, 2010 ). Type I IFNs play the critical signaling role in some well researched adjuvants, including Th1 and CTL polarized types (Proietti et al, 2002 ; McBride et al, 2006 ).…”

Low‐dose oral interferon alpha as prophylaxis against viral respiratory illness: a double‐blind, parallel controlled trial during an influenza pandemic year

“…It is hypothesized that IFN delivered by the oral route binds to receptors on specialized cells in the oral and/or pharyngeal cavity and elicits a therapeutic immune response without the need for delivery of exogenous IFN into the systemic circulation . Oral administration of low‐dose recombinant IFN 1 has been shown to produce immunomodulatory effects in animal studies and human clinical trials, and to reduce influenza mortality in a mouse model . It has been well tolerated in these trials with no evidence of significant adverse effects.…”