Title

Immunomodulatory effects of in vitro exposure to organochlorine mixtures in marine mammals, humans, and mice

Date of Completion

January 2004

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

The field of marine mammal immunotoxicology is a relatively young discipline, which studies the toxic effects of compounds, both natural and anthropogenic, on the immune system of marine mammals. Due to factors such as feeding at the top of the food chain, maintaining lipid reservoirs (blubber), having long life spans, and inhabiting polluted waters, these animals are exposed to, and accumulate, high concentrations of environmental contaminants, notably, persistent organochlorine pollutants (POPs), including polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (PCDDs). These compounds are known to be immunotoxic in laboratory animals and accumulating evidence suggests the same is true for marine mammals. Though cause and effect relationships between these compounds and health effects in marine mammals have yet to be fully defined, evidence of effects such as reproductive impairment, endocrine disruption, and immune modulation support the hypothesis POPs are detrimental to the overall health of marine mammals around the world. This study focused on the immunomodulatory effects of organochlorines on marine mammal innate immune functions, including phagocytosis and respiratory burst. Calcium mobilization, an early event in cell signaling, is also investigated as a possible mechanism of action for the modulation of phagocytosis. In addition, this study tested the immunomodulatory potential of mixtures of organochlorines compared to that of individual compounds, and compared the relative sensitivity of different species of marine mammals, humans and t B6C3F1 mice, a strain commonly used for immunotoxicological studies. The toxic equivalency (TEQ) approach, used to determine the toxicity of an organochlorine mixture, was employed to determine its relevance to marine mammal immunotoxicity studies. It was concluded that (1) different species of marine mammals, humans and B6C3F1 mice were not equally sensitive to the effects of organochlorines on phagocytosis or the respiratory burst, (2) interaction of organochlorines in a mixture were not always additive, (3) coplanar and non-coplanar PCBs did not exert similar effects, and (4) calcium mobilization may have partially mediated the effects of organochlorines on phagocytosis. A better understanding of the immunomodulatory effects of environmental contaminants will be useful for future assessment of the possible impact of those pollutants on the health of marine mammals and humans, as well as other species, and managing the risks associated with exposure to the ubiquitous organochlorines in general. ^