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

• Published in: Veterinary immunology and immunopathology 2016-04, Vol.172, p.64-71
• Main Authors: Mamber, Stephen W., Lins, Jeremy, Gurel, Volkan, Hutcheson, David P., Pinedo, Pablo, Bechtol, David, Krakowka, Steven, Fields-Henderson, Rachel, Cummins, Joseph M.
• Format: Article
• Language: English
• Subjects: Animals; Autoimmune and inflammatory response genes; Autoimmunity - drug effects; Autoimmunity - genetics; Cattle; Cattle-bovine; Creatine Kinase - blood; Cytokines - genetics; Dose-Response Relationship, Drug; Foot-and-mouth disease (FMD); Foot-and-mouth disease virus; Gene Expression - drug effects; IFN–stimulated genes (ISGs); Interferon (IFN) alpha (α); Interferon-alpha - administration & dosage; Interferon-alpha - therapeutic use; KEGG pathway analysis; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Male; Receptors, Cytokine - genetics
• ISSN: 0165-2427; 1873-2534
• DOI: 10.1016/j.vetimm.2016.03.006

•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 8h later. Blood was collected at 0, 8 and 24h 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 8h, 50 and 200 units of oral IFN induced significant (P