Evidence for the Immunostimulatory Effects of Low-Dose Orally Delivered Human IFN- α in Cattle

Orally delivered interferon-α (IFN-α) has been associated with systemic protection against various disorders in humans and animals. In an attempt to understand how IFN-α delivers a systemic signal following its local oral administration, the present study aimed at identifying genes differentially regulated in bovine peripheral blood through the use of cDNA microarrays following oral therapy with IFN-α. We identified thousands of genes to be IFN-α regulated. Of these, about 8.5% had a minimum 4-fold degree of change, the majority of which represented novel IFN-stimulated genes (ISG). Several upregulated ISGs were transcripts with key and diverse biologic functions, including antigen processing and presentation, leukocyte migration, lymphocyte activation, immune effector and modulation functions, apoptosis, and hematopoiesis. Interestingly, IFN-α expression itself was not modulated in bovine peripheral blood, suggesting that the blood levels of IFN-α are not the hallmark of the immunostimulatory effects of oral IFN-α therapy. Rather, IFN-α seems to interact with local mucosal lymphoid cells in the gastrointestinal tract. This interaction may initiate a signaling cascade eventually leading to the transcriptional induction of ISGs, which in turn encode immunostimulatoiry proteins. Thus, ISGs, through the proteins they encode, may potentially perform critical immune modulation functions.