MECHANISM OF THE IMMUNOTOXIC EFFECTS OF CHLORDANE

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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.