Immunomodulatory Effects of in Vitro Exposure to Organochlorines on T-Cell Proliferation in Marine Mammals and Mice

Abstract

Marine mammals bioaccumulate various environmental contaminants such as organochlorines (OCs), which biomagnify via the food web. While the immunomodulatory effects of individual OCs have been studied, the effects of mixtures are not well understood. The immunomodulatory effects of polychlorinated biphenyl (PCB) 138, 153, 169, and 180 as well as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and all possible mixtures were examined in marine mammals and mice. Lymphocyte proliferation was significantly modulated by OCs in all species tested, mostly by non-coplanar PCBs, as shown using regression analyses. Correlation analyses showed significant correlations (interpreted as additive effects) between OCs in mice, killer whales, and Steller sea lions. Nonadditive synergistic and antagonistic interactions between OCs were detected in most of the species tested. Toxic equivalency (TEQ) values used for OC toxicity assessment failed to predict the immunomodulatory effects measured in mice and marine mammals. The commonly used mouse model failed to predict immunomodulatory effects in other species. Clustering data suggested that phylogeny does not predict toxicity of OCs. Overall, our data suggest the presence of species-specific sensitivities to different mixtures, in which OCs interactions may be complex and that may exert their effects through dioxinlike or dioxin-independent pathways. Lastly, lymphocyte proliferation, an important part of adaptive immunity, was significantly modulated in mice and marine mammals, suggesting the possibility of increased susceptibility to diseases. These findings will be useful to better characterize the risk associated with OC exposure and possibly lead to new conservation and management strategies.

Acknowledgements

We thank the staffs at Mystic Aquarium, Sea World at San Diego and San Antonio, U.S. Navy Marine Mammal Program, Shedd Aquarium, Marine Environmental Research Institute, and California Department of Fish and Game for providing the marine mammal blood samples. Funding for this work was provided by the NCER/STAR program of the U.S. Environmental Protection Agency, with initial funding from the University of Connecticut Research Foundation. Although the research described in this article has been funded wholly or in part by the United States Environmental Protection Agency's National Center for Environmental Research (NCER) STAR Program through grant R-82836101-0 to Sylvain De Guise, it has not been subjected to the agency's required peer and policy review and therefore does not necessarily reflect the views of the agency and no official endorsement should be inferred.