Immunological changes of chronic oral exposure to depleted uranium in mice

- Mice received dietary DU for 4 months to assess the immunological changes.
- After ingestion of DU at lower doses, the influences were slight.
- With increasing DU doses of exposure, the innate immune function tended to decrease.
- Also, the cellular and humoral immune functions tended to dysregulation.
- DU may cause a systematic shift of Th1 cytokines to Th2 cytokines.

Direct ingestion of contaminated soil by depleted uranium (DU) might lead to internal exposure to DU by local populations through hand contamination. The purpose of this study was to assess the immunological changes of long-term exposure to various doses of DU in mice. Three-week-old Kunming mice were divided into the following 4 groups based on the various feeding doses (containing DU): 0 (control group), 3 (DU3 group), 30 (DU30 group), and 300 mg/kg feed (DU300 group). After 4 months of exposure, in the DU300 group, the innate immune function decreased, manifesting as decreased secretion of nitric oxide, interleukin (IL)-1β, IL-18, and tumour necrosis factor (TNF)-α in the peritoneal macrophages, as well as reduced cytotoxicity of the splenic natural killer cells. Moreover, the cellular and humoral immune functions were abnormal, as manifested by decreased proliferation of the splenic T cells, proportion of the cluster of differentiation (CD) 3+ cells, ratio of CD4+/CD8+ cells and delayed-type hypersensitivity, and increased proliferation of the splenic B cells, total serum immunoglobin (Ig) G and IgE, and proportion of splenic mIgM+mIgD+ cells. Through stimulation, the secretion levels of interferon (IFN)-γ and TNF-α in the splenic cells were reduced, and the levels of IL-4 and IL-10 were increased. By comparison, in the DU30 and DU3 groups, the effects were either minor or indiscernible. In conclusions, chronic intake of higher doses of DU (300 mg/kg) had a significant impact on the immune function, most likely due to an imbalance in T helper (Th) 1 and Th2 cytokines.