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.
Highlights
Injections of interferon alpha (IFNα) by intravenous, subcutaneous, intramuscular, and intraperitoneal routes of administration have all been used to treat numerous diseases [1,2]
In another study of Mx1+/+ mice, it was reported that a single intranasal dose of 500,000 IU of HuIFNαB/D, given 10 hours before the virus challenge, protected mice against a lethal challenge with 100 LD50 of influenza A/PR/8/34 virus; all control mice died within five days
TNFα expression was found to be significantly upregulated in the fish treated with Human IFNα (HuIFNα) when analyzed on days 1 and 5 post-treatment expression of IL-10 was enhanced in HuIFNα-treated fish when observed on days 1, 3 and 5 post-treatment [18]
Summary
Injections of interferon alpha (IFNα) by intravenous, subcutaneous, intramuscular, and intraperitoneal routes of administration have all been used to treat numerous diseases [1,2]. The investigators of these studies did not deliver the IFNα by the oral mucosal route Instead, they bypassed the oral cavity by administering the IFNα by gavage directly into the stomach. The presence of detectable IFNα in the blood may not be required or even desired for IFNα administered by the oral mucosal route to activate systemic host protective mechanisms. The oral mucosal route of administration for IFNα may offer potential therapeutic benefits by inducing systemic host protective mechanisms. This innate immune response involves the nasal production of Type I IFNs (α and β) followed by their binding to oromucosal surfaces, which in turn activates both local and systemic responses Based on this innate defense mechanism, IFNα and IFNβ have been administered orally to humans in various contexts and these studies are reviewed in this article.
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