The immunotoxic potential of many classes of environmental contaminants has been well established in laboratory studies, with much attention being focussed on aryl hydrocarbon (Ah)-receptor binding polychlorinated biphenyl (PCB), polychlorinated dibenzo-p-dioxin (PCDD), and polychlorinated dibenzofuran (PCDF) congeners. In a semi-field study, we previously showed that harbour seals (Phoca vitulina) fed herring from the contaminated Baltic Sea had lower natural killer cell activity, T-lymphocyte functionality and delayed-type hypersensitivity responses than seals fed herring from the relatively uncontaminated Atlantic Ocean. While ethical and practical constraints preclude in-depth studies in seals, specific reagents and a wider array of immune function tests allow such studies in laboratory rats. We therefore carried out a feeding study in rats aimed at extending our observations of contaminant-induced immunosuppression in harbour seals. The same two herring batches used in the seal study were freeze-dried, supplemented and fed. to female adult PVG rats for a period of 4 1/4 months. Daily contaminant intakes of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalents (TEQ) were estimated to be 0.3 ng/kg body weight and 1.6 ng/kg in the Atlantic and Baltic groups, respectively. At the end of the feeding experiment, no contaminant-related changes in spleen CD4+/CD8+cellularity, natural killer cell activity, or mitogen-induced proliferative responses of thymus or spleen cells could be detected. However, total thymocyte numbers and thymus CD4+/CD8+ratios were reduced in the Baltic group. A novel model was established to assess the specific T-cell response to rat cytomegalovirus (RCMV). When applied to the feeding study, no differences between the Atlantic and Baltic groups in the RCMV-induced proliferative T-lymphocyte responses could be detected, but virus titres in salivary glands of infected rats of the Baltic Sea group were higher. These elevated RCMV titres and changes in thymus cellularity suggest that the dietary exposure to low levels of contaminants may have been immunotoxic at a level which our immune function test could not otherwise detect. While the herring diet per se appeared to have an effect on several immune function parameters, lower plasma thyroid hormone levels in the Baltic Sea group of rats confirmed that exposure to the environmental mixture of contaminants led to adverse PHAH-related health effects.

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Archives of Toxicology
Department of Virology

Ross, P., van Loveren, H., de Swart, R., van der Vliet, H., de Klerk, A., Timmerman, H., … Osterhaus, A. (1996). Host resistance to rat cytomegalovirus (RCMV) and immune function in adult PVG rats fed herring from the contaminated Baltic Sea. Archives of Toxicology, 70(10), 661–671. doi:10.1007/s002040050326