, 2011). However, to the best of our knowledge, no immunological analyses of the uranium-exposed population have been conducted. Finally, long-term exposure to DU led to significant changes in the level of cytokines released by stimulated splenic cells in the mice. In general, when the DU dose in feed was

higher than 30 mg/kg, the chronic exposure decreased the expression of Th1 cytokines (IFN- γ, TNF-α) and increased the expression of Th2 cytokines (IL-4, IL-10) with a shift of Th1 cytokines to Th2 cytokines. To the best of our knowledge (Mosmann and Coffman, 1989 and Abbas et al., 1996), Th1 cells mediate the immune response related to cytotoxicity and local inflammation and are involved in the formation of cellular immunity and delayed-type hypersensitivity. Trametinib Th1 cells also activate Nutlin-3a order iNOS in macrophages to promote their secretion of NO, thereby yielding the above-described results, including decreased proliferative ability of T cells, decreased

responsiveness of DTH, and macrophage dysfunction—which are adequately explained by the inhibition of Th1 cytokines. The main function of Th2 cells is to stimulate B cells to proliferate and, subsequently, to generate antibodies, the production of which is associated with humoral immunity. Th2 cells may assist the mouse B cells to synthesise IgA, IgG, and IgE and may negatively regulate cytotoxic T cells (CTL) and

NK cells. Therefore, the increased levels of Th2 cytokines offers a good explanation for the increase in the total serum IgG and IgE levels, as well as the weakened cytotoxic effect of the NK cells. Similar to the results of this Tangeritin study, numerous studies (Heo et al., 1997, Dietert and Piepenbrink, 2006 and Gao et al., 2007) have demonstrated that exposure to low doses of lead causes a significant shift of Th1 cytokines to Th2 cytokines. However, chronic ingestion of DU by drinking water (40 mg/l), did not lead to modifications in the cytokine gene expression in Peyer’s patches (Dublineau et al., 2006). The differences may be due to the different exposure routes and evaluation tissue. In addition, before determination of cytokine, splenic cells were stimulated with ConA or PMA and ionomycin, which would increase the differences between groups. The limitation of the present study is that only one time point was evaluated; thus, the results do not reflect the dynamic changes in immune function based on the age of the animal and the exposure time to DU. In summary, after 4 months of exposure to low doses of DU (lower than 30 mg/kg) through the diet in young mice, the impact of DU exposure on the immune function of the body was relatively small.