Effects of an environmentally relevant PCB-mixture on immune function, clinical chemistry, and thyroid hormone levels in adult female B₆C₃F₁ mice

ABSTRACT

Polychlorinated biphenyls (PCBs) have been assessed for immunotoxicity; however, humans and wildlife are exposed to multiple PCBs environmentally. Therefore, the aim of this study was to examine the effects of a complex 37 PCB congener mixture identified in blubber specific to dolphins residing in the estuarine waters of Charleston, South Carolina. Immunotoxicity was determined in adult female B₆C₃F₁ mice by assessing lymphocyte proliferation, splenic and thymic immunophenotypes, and IgM production. Mice were exposed via oral gavage to the PCB-mixture (0, 1.8, 3.6, 7.1, or 14.3 mg/kg/day) for 28 days to yield a targeted total administered dose (TAD) 0, 50, 100, 200, or 400 mg/kg. Significant increased liver weight occurred at the highest treatment. IgM production was suppressed compared to control for all treatments. Numbers of thymic CD4+/CD8+, CD4-/CD8-, and CD4+/CD8- cells were not altered, but numbers of thymic CD4-/CD8+ cells were significantly increased in the highest treatment. Lymphocyte proliferation was not markedly affected by any treatment. The numbers of splenic CD4/CD8 T-cells or MHCII+ cells were not significantly changed. Humoral immunity using the plaque-forming cell assay for determining the specific IgM antibody-forming cell response appeared to be the most sensitive endpoint affected. As the lowest concentration tested resulted in decreased IgM production and total and free thyroxine (T₄) serum levels a NOAEL was not identified. The calculated ED₅₀ for suppression of IgM production was 2.4 mg/kg/day.

KEYWORDS:

• Polychlorinated biphenyls (PCB)-mixture
• bottlenose dolphin
• B₆C₃F₁ mice
• immune
• thyroid hormone

Acknowledgments

The authors would like to thank Dr. Gary Gilkeson and Ms. Jackie EuDaly, Medical University of South Carolina (MUSC), for their technical assistance. We acknowledge the MUSC and the Hollings Cancer Center for their support of the Flow Cytometry & Cell Sorting Shared Resource Facility. Research was supported through NOAA/NCCOS/CCEHBR and the NOAA Fisheries Marine Mammal Health and Stranding Response Program.

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The scientific results and conclusions, as well as any opinions expressed herein, are those of the author(s) and do not necessarily reflect the views of NOAA or the Department of Commerce. The mention of any commercial product is not meant as an endorsement by the Agency or Department.

Additional information

Funding

This work was supported by the National Oceanic and Atmospheric Administration.