MECHANISM OF THE IMMUNOTOXIC EFFECTS OF CHLORDANE

氯丹是一种氯代烃类杀虫剂，通常用于白蚁。 对住宅和商业建筑的控制及其极端 长半衰期已成为世界范围内的普遍现象。例如， 氯丹的代谢物和残留物已被证明存在于 一些动物物种(1，2)的组织以及 美国和其他国家的哺乳期人类(2)。我们的实验室(3-6) 有报道称，小鼠在子宫内暴露于氯丹会导致 迟发性超敏反应(DTH)的显著抑郁和增加 成人感染后对A/PR/8/34流感病毒的生存能力。 氯丹介导的传染病抵抗力变化 似乎与许多免疫学变化有关，包括 潜伏期。这项建议的目的是更详细地调查 宫内接触氯丹的免疫学效应及其影响 这些影响对一种传染病的发病机制也是 无处不在的，流感。最初，我们打算确定 宫内氯丹暴露对迟发型超敏反应的抑制作用 在细胞和可溶性产物的传入和传出阶段 潜伏期。我们还将通过以下方式确定清除病毒的机制 测量一系列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，氯丹可能会影响 调节迟发型超敏反应的特异性T抑制细胞，这也将是 调查过了。 我们将启动一系列实验，以确定小鼠， 年轻时接触氯丹，他们的迟发型超敏反应也有明显变化 以及它们抵抗流感感染的能力。我们将决定 是否以及这样的影响可能是由于病毒动力学的变化 在肺中复制，如果免疫反应在相同的 方法就像宫内氯丹治疗一样。

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.