Ross P S, Van Loveren H, de Swart R L, van der Vliet H, de Klerk A, Timmerman H H, van Binnendijk R, Brouwer A, Vos J G, Osterhaus A D
Seal Rehabilitation and Research Centre, Pieterburen, The Netherlands.
Arch Toxicol. 1996;70(10):661-71. doi: 10.1007/s002040050326.
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 1/2 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.
许多种类的环境污染物的免疫毒性潜力在实验室研究中已得到充分证实,其中多氯联苯(PCB)、多氯二苯并对二恶英(PCDD)和多氯二苯并呋喃(PCDF)同系物等芳烃(Ah)受体结合物备受关注。在一项半野外研究中,我们先前发现,食用受污染波罗的海鲱鱼的港海豹(Phoca vitulina),其自然杀伤细胞活性、T淋巴细胞功能和迟发型超敏反应,均低于食用相对未受污染大西洋鲱鱼的海豹。虽然伦理和实际限制妨碍了对海豹进行深入研究,但特定试剂和更广泛的免疫功能测试使得能够在实验大鼠身上开展此类研究。因此,我们对大鼠进行了一项喂养研究,旨在扩展我们对污染物诱导港海豹免疫抑制的观察。海豹研究中使用的同一两批鲱鱼经过冷冻干燥、添加成分后,喂给成年雌性PVG大鼠,为期4个半月。据估计,大西洋组和波罗的海组大鼠每日摄入的2,3,7,8 - 四氯二苯并对二恶英(TCDD)毒性当量(TEQ)分别为0.3 ng/kg体重和1.6 ng/kg。在喂养实验结束时,未检测到脾脏CD4+/CD8+细胞数量、自然杀伤细胞活性或胸腺或脾脏细胞有丝分裂原诱导的增殖反应出现与污染物相关的变化。然而,波罗的海组大鼠的胸腺细胞总数和胸腺CD4+/CD8+比值降低。建立了一种新模型来评估大鼠对大鼠巨细胞病毒(RCMV)的特异性T细胞反应。应用于喂养研究时,未检测到大西洋组和波罗的海组在RCMV诱导的增殖性T淋巴细胞反应方面存在差异,但波罗的海组受感染大鼠唾液腺中的病毒滴度较高。这些升高的RCMV滴度和胸腺细胞数量的变化表明,饮食中低水平污染物暴露可能在我们的免疫功能测试无法检测到的水平上具有免疫毒性。虽然鲱鱼饮食本身似乎对几个免疫功能参数有影响,但波罗的海组大鼠较低的血浆甲状腺激素水平证实,暴露于环境污染物混合物会导致与多环芳烃相关的不良健康影响。