Long-term effects of mycophenolic acid on the immunoglobulin and inflammatory marker-gene expression in sheep white blood cells

Abstract

Mycophenolic acid (MPA) is an active secondary metabolite from Penicillium roqueforti found frequently in contaminated silage for sheep in a temperate climate. The main objective of this study was to evaluate the long-term effect of MPA on mRNA expression of immunoglobulins and cytokines in white blood cells (WBC). Administration of 300 mg MPA per sheep and day was compared with untreated animals for 9 weeks. As immunological markers, the expression levels of immunoglobulins (Igα, Igε, Igμ and Igγ2) and pro-inflammatory cytokines (TNFα, IL1α, IL1β, IL2 and IL6) in WBC were determined. A real-time reverse-transcription polymerase chain reaction (qRT-PCR) with an efficiency-corrected quantification model, named REST, was used to quantify the mRNA expression changes. No effects of MPA administration were found on leucocyte total RNA content. No significant influence of MPA on Igα, Igμ, Igε, Igγ2 gene expression could be found. IL2 and IL6 showed a constant expression pattern over the entire time of the investigation. TNFα was up-regulated in week 1, while down-regulation was detected for IL1α mRNA expression in weeks 2 and 5. According to our data, oral uptake of silage extremely contaminated with a very high concentration of MPA did not have a significant influence on immunoglobulins and cytokines in WBC.