High IL-1α Production Was Induced in the WBN/Kob- Type 2 Diabetes Mellitus Rat Model and Inhibited by Infection.

The novel WBN/Kob- () congenic rat strain is considered a useful rat model of type 2 diabetes mellitus (T2DM). Accumulating findings suggest that low-grade inflammation is a causative factor in T2DM and that circulating levels of inflammatory cytokines are associated with insulin resistance. However, inflammatory cytokine profiles and their correlations with T2DM development/ progression in rats have not been studied. In this study, we found that the rats had considerably high plasma levels of interleukin (IL)-1α. Abundant cecal IL-1α mRNA expression and cecal inflammation with infiltrating IL-1α-producing macrophages was observed in rats. Bone marrow derived macrophages from rats expressed high levels of IL-1α upon lipopolysaccharide stimulation. Furthermore, infection, which delays the onset of T2DM, reduced both plasma and cecal IL-1α levels in rats. These results suggest that macrophage infiltration and IL-1α secretion comprise an important part of T2DM development and that infection inhibits pro-inflammatory cytokine expression in rats.