Short-term effects of depleted uranium on immune status in rat intestine

Dublineau I, Grison S, Linard C, Baudelin C, Dudoignon N, Souidi M, Marquette C,
Paquet F, Aigueperse J and Gourmelon P. J. Toxicol. Environmental Health, 69: 1613-1628, 2006

In the event of ingestion, the digestive tract is the first biological system exposed to depleted uranium (DU) intake via the intestinal lumen. However, little research has addressed the biological consequences of a contamination with depleted uranium on intestinal properties such as the barrier function and/or the immune status of this tissue. The aim of this study was to determine if the ingestion of depleted uranium led to changes in the gut immune system of the intestine. The experiments were performed at 1 and 3 days following a per os administration of DU to rats at sublethal dose (204 mg/kg). Several parameters refering to the immune status, such as gene and protein expressions of cytokines and chemokines, and localization and density of immune cell populations, were assessed in the intestine. In addition, the overall toxicity of DU on the small intestine was estimated in this study, with histological appearance, proliferation rate, differentiation pattern and apoptosis process.

Firstly, the results of this study indicated that DU was not toxic for the intestine, as measured by the proliferation, differentiation and apoptosis processes. Concerning the immune properties of the intestine, the ingestion of depleted uranium induced some changes in the production of chemokines and in the expression of cytokines. A diminished production of MCP-1 was noted at one day post-exposure. At three days, the increased gene expression of IFNg was associated with an enhanced mRNA level of Fas ligand, suggesting an activation of the apoptosis pathway. However, no increased apoptotic cells were observed at three days in the contaminated animals. There were no changes in the localization and density of neutrophils, helper T lymphocytes and cytotoxic T lymphocytes after DU administration. In conclusion, these results suggest that depleted uranium is not toxic for the intestine after acute exposure. Nevertheless, DU seems to modulate the expression and/or production of cytokines (IFNg) and chemokines (MCP-1)in the intestine. Further experiments need to be performed to determine if a chronic contamination at low dose leads in the long term to 3 modifications of cytokines/chemokines patterns, and to subsequent changes in immune response of the intestine.