MECHANISM OF THE IMMUNOTOXIC EFFECTS OF CHLORDANE

百菌清是一种氯代烃类农药，常用于白蚁 住宅和商业建筑物的管制， 长半衰期在世界范围内变得普遍。 比如说 代谢物和残留物的氯霉素已被证明存在于 许多动物物种的组织（1，2）以及 美国和其他国家的哺乳期人类（2）。 我们的实验室（3-6） 曾报道，在子宫内暴露于氯霉素的小鼠， 在迟发型超敏反应（DTH）和增加的显着抑制 在成人感染甲型/PR/8/34流感病毒后的存活率。 氯丹介导的对感染性疾病抗性的改变 似乎与许多免疫学变化有关，包括 DTH。 本提案的目的是更详细地调查 子宫内接触氯霉素的免疫学效应以及 这些对传染病发病机制的影响， 无处不在的流感 首先，我们打算确定 通过测试氯丹效应，通过子宫内氯丹暴露抑制DTH 的传入和传出相的细胞和可溶性产物， DTH。 我们还将确定清除病毒的机制， 测量许多病毒特异性免疫参数，例如 细胞毒性和干扰素。 我们的数据表明，氯霉素可能会影响 特异性T抑制细胞，调节DTH，这也将是 研究了 我们将启动一系列实验， 暴露于氯丹作为年轻的成年人，也表现出变化，在他们的DTH 以及抵抗流感感染的能力。 我们将确定 这种效应是否可能是由于病毒的动力学变化， 如果免疫反应受到影响， 就像在子宫内使用氯吡格雷一样。

Chlordane is a chlorinated hydrocarbon pesticide commonly used for termite control for residential and commercial structures and with its extremely long half-life has become prevalent world-wide. For example, the metabolites and residues of chlordane have been shown to be present in the tissues of a number of animal species (1, 2) as well as the milk of lactating humans in the U.S. and other countries (2). Our laboratory (3-6) has reported that in utero exposure of mice to chlordane results in a dramatic depression in delayed-type hypersensitivity (DTH) and an increase in survival to influenza A/PR/8/34 virus following infection as adults. The chlordane-mediated alteration in resistance to infectious disease appears to be related to a number of immunological changes, including the DTH. The purpose of this proposal is to investigate in greater detail the immunological effects of in utero exposure to chlordane and the impact of these effects on the pathogenesis of an infectious disease which is also ubiquitous, influenza. Initially, we intend to determine the mechanism of DTH depression by in utero chlordane exposure by testing chlordane effects on the cells and soluble products of the afferent and efferent phases of DTH. We will also determine the mechanism of clearance of the virus by measuring a number of viral specific immune parameters, such as cytotoxicity and interferon. Our data suggest that chlordane may affect specific T suppressor cells, which regulate DTH and this will also be investigated. We will initiate a series of experiments designed to determine if mice, exposed to chlordane as young adults, also manifest changes in their DTH and in their ability to resist influenza infection. We will determine whether and such effects might be due to changes in the kinetics of viral replication in the lung and if immune reactions are affected in the same way as in utero chlordane treatment.