The food born mycotoxin deoxynivalenol induces low-grade inflammation in mice in the absence of observed-adverse effects

• The present work shows that sub-chronic low doses DON exposure induces an increase in cytokine mRNAs expression in both peripheral organs and brain.
• The present work demonstrates that sub-chronic low doses DON exposure provokes histological liver alterations.
• The present work provides the first demonstration that sub-chronic administration of low DON doses in mice results in a low-grade inflammation state.
• The present work questions about the harmlessness of chronic human dietary DON exposure and challenges the provisional maximum tolerable daily intake (PMTDI) of 1 μg/kg bw.

ScopeDeoxynivalenol (DON) is the most common fungi toxin contaminating cereals and cereal-derived products. High consumption of DON is implicated in mycotoxicoses and causes a set of symptoms including diarrhea, vomiting, reduced weight gain or immunologic effects. However, such clinical intoxications are rare in humans, who are most frequently, exposed to low DON doses without developing acute symptoms. The adverse effect of chronically consumed low DON doses can not be totally excluded. Using a mouse model, we evaluated the impact on inflammatory status of subchronic administration of DON given at doses comparable to the daily human consumption.Methods and resultsThe inflammatory status was evaluated in mice receiving 1, 2.5 or 25 μg/kg bw/day DON during a 10 or 30 days period. The systemic interleukin-1 beta (IL-1β) concentrations were evaluated by Elisa and inflammatory biomarker mRNA expressions were quantified by qPCR within brain structures and peripheral organs. While DON intake failed to modify physiological markers, we observed a systemic IL-1β increase and a modulation of pro-inflammatory gene expression in brain structures, liver, duodenum and adipose tissue.ConclusionWe bring here the first evidence that subchronic DON intake, at doses that match daily human intake, induces, in a murine model, a central and peripheral low grade inflammation.