Protective Effect of Orally Administered Human Interferon (HuIFN)-α against Systemic Listeria monocytogenes Infection and a Practical Advantage of HuIFN-α Derived from Transgenic Potato Plant

Abstract

Type I interferon (IFN-alpha/beta) is the first cytokine used for clinical applications against viral and neoplasmic diseases. Usually, it is administrated by subcutaneous and intramuscular injection, but several studies have reported that orally administered Type I IFN is also effective against viral and autoimmune diseases. Therefore, we examined whether orally administered human IFN (HuIFN)-alpha can augment protection against systemic bacterial infection using L. monocytogenes infection in mice as an experimental model. Daily oral administrations for 6 days of 1000 international units (IU) of purified natural HuIFN-alpha reduced bacterial burden in spleen and liver from L. monocytogenes-infected mice. This effect was observed in the middle phase of L. monocytogenes infection, but not in the early phase of the infection. The effects of the oral administration of HuIFN-alpha expressed in potato plant were also examined. Daily oral administrations of extracts of the transgenic potato tuber for 6 days decreased bacterial burden in the spleen. Lower doses of HuIFN-alpha in the extracts (20 IU/mouse daily) exerted a protective effect at almost the same level as that achieved by the administration of 1000 IU of HuIFN-alpha. This result may be due to the 'bioencapsulation' effect for HuIFN-alpha by plant compartmentalization, which is one of the advantages of the plant expression system over other expression systems of recombinant proteins. Our present observation indicates the transgenic plants expressing cytokines can be used as feed/food and their additives to enhance natural immune responses in humans and animals.