The immunotoxicity of natural and depleted uranium: From cells to people

Abstract

Uranium is a naturally occurring element found in the environment as a mixture of isotopes with differing radioactive properties. Enrichment of mined material results in depleted uranium waste with substantially reduced radioactivity but retains the capacity for chemical toxicity. Uranium mine and milling waste are dispersed by wind and rain leading to environmental exposures through soil, air, and water contamination. Uranium exposure is associated with numerous adverse health outcomes in humans, yet there is limited understanding of the effects of depleted uranium on the immune system. The purpose of this review is to summarize findings on uranium immunotoxicity obtained from cell, rodent and human population studies. We also highlight how each model contributes to an understanding of mechanisms that lead to immunotoxicity and limitations inherent within each system. Information from population, animal, and laboratory studies will be needed to significantly expand our knowledge of the contributions of depleted uranium to immune dysregulation, which may then inform prevention or intervention measures for exposed communities.

Keywords: Human exposure; Immunotoxicity; Uranium.

Fig. 1.

Summary of results from in vitro studies. The first column lists the most commonly used soluble uranium forms. The second column lists the species of origin and target immune cells used for the in vitro studies. The third column summarizes results from the in vitro treatments. The fourth column contains the corresponding results references. Squares under the stated effect correspond to the target immune cells displaying the response (purple = macrophages; blue = T-cells; pink = monocytes; orange = human mixed lymphocytes).

Fig. 2.

Summary of in vivo tissue distribution and immune cell function alterations by dose and model species. Grey and colored boxes create quadrants where red indicates exposure to higher uranium doses and blue indicates exposure to lower uranium doses. Column one lists tissues where uranium accumulation was detected in the corresponding species. Accumulation of uranium in immune tissues has been reported by Bolt et al., 2018 and Hao et al., 2013. Column two lists the changes in immune cell function that were measured with either higher (red quadrant) or lower (blue quadrant) doses in the corresponding species (references listed below each immune cell function).

Fig. 3.

Summary of molecular changes observed in target immune cells due to uranium exposure and potential health outcomes. Column one lists target immune cell categories including lymphocytes (T-cells, B-cells, and natural killer cells), leukocytes (all white blood cells) and peripheral blood mononuclear cells or PBMCs (T-cells, B-cells, natural killer cells and dendritic cells). Column two summarizes the effects reported for the target immune cells (references listed below each reported immune cell effect). Column three lists potential health outcomes that may arise due to reported effects on target immune cells.