Low-dose oral interferon modulates expression of inflammatory and autoimmune genes in cattle

• Low-dose oral interferon (IFN) modulated expression of genes in cattle PBMC.
• Placebo and 800 units of IFN were similar in their negligible effects on genes.
• Significant changes in expression of 42 of 92 genes were noted with 50–200 units.
• Direct evidence of immune response systemic modulation by low doses of oral IFN in cattle.

While the safety and efficacy profiles of orally administered bovine interferon (IFN) alpha have been documented, the mechanism(s) that result in clinical benefits remain elusive. One approach to delineating the molecular pathways of IFN efficacy is through the use of gene expression profiling technologies. In this proof-of-concept study, different (0, 50, 200 and 800 units) oral doses of natural bovine IFN (type I) were tested in cattle to determine if oral IFN altered the expression of genes that may be pivotal to the development of systemic resistance to viral infections such as foot-and-mouth disease (FMD). Oral IFN was administered twice: Time 0 and 8 h later. Blood was collected at 0, 8 and 24 h after the first IFN administration, and DNA isolated from peripheral blood mononuclear cells (PBMCs) was employed in quantitative polymerase chain reaction (qPCR) microarray assays. Within 8 h, 50 and 200 units of oral IFN induced significant (P < 0.05) changes in expression of 41 of 92 tested autoimmune and inflammatory response-associated genes. These data suggest that orally administered IFN is a viable approach for providing short-term antiviral immunity to livestock exposed to viruses such as FMD virus (FMDV) until such a time that an effective vaccine can be produced and distributed to producers.