You are here:
SUSCEPTIBILITY OF THE DEVELOPING IMMUNE SYSTEM OF THE RAT TO IMMUNOSUPPRESSION BY THE PESTICIDE HEPTACHLOR
Citation:
Smialowicz, R J., W C. Williams, AND C B. Copeland. SUSCEPTIBILITY OF THE DEVELOPING IMMUNE SYSTEM OF THE RAT TO IMMUNOSUPPRESSION BY THE PESTICIDE HEPTACHLOR. Presented at Long-Range Research Initiative (LRI) Annual Science Meeting, American Chemistry Council, Herndon, VA, June 24-25, 2003.
Description:
Determination of the Potential Susceptibility of the Developing Immune System of the Rat to Immunosuppression by the Pesticide Heptachlor
R.J. Smialowicz1 W.C. Williams1, C.B. Copeland1, and R.A. Matulka2
1Office of Research and Development, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, 2University of North Carolina at Chapel Hill, Curriculum in Toxicology
A panel of in vivo, ex vivo and in vitro assays were employed to determine whether the developing (i.e., early gestation to pre-puberty) rat immune system exhibits increased susceptibility to immunosuppression by heptachlor (HE) compared to young adults. Dams were dosed from gestational day 6 (GD6) through post-natal day 21 (PND21), at which time the pups were weaned and dosed directly until PND42. Young adult rats (6-weeks-old) were dosed for 3 weeks. HE was administered in corn oil by gavage at 0, 0.03, 0.1, 0.3, 1.0 and 3.0 mg/kg/day. Male and female rats were tested for the delayed type hypersensitivity (DTH) response, phagocytic activity of macrophages, splenic natural killer (NK) cell activity, phenotypic analysis of splenic and thymic cells, and antibody response to sheep red blood cells (SRBCs). Exposure to HE, either during immune system development or early adulthood, did not alter body, spleen or thymus weights, NK cell activity, DTH response, IgM or IgG anti-SRBC response, or macrophage phagocytosis in either males or females. Phenotypic analysis of splenic CD5+ (pan T cells), CD4+ (helper T cells), CD8+ (cytotoxic T cells) and CD161+ (NK cells), and thymic CD4+ cells indicated no alteration in these cells compared to controls. However, percentages of thymic CD5+ cells, in rats exposed during immune development, were suppressed at 1.0 and 3.0, and at 3.0 mg HE/kg/day in males and females, respectively. In young adult rats, the percentage of thymic CD5+ cells was also suppressed at 3.0 mg HE/kg/d in males and at 0.3 -3.0 mg HE/kg/d in females. A decrease was observed in CD4+/CD8+ thymic cells at 3.0 mg HE/kg/d in females, and at 1.0 and 3.0 mg HE/kg/d in males exposed during immune development. Furthermore, in adult exposed rats the percentage of CD4+/CD8+ thymic cells was decreased at 1.0 and 3.0, and at 3.0 mg HE/kg/d, in males and females respectively. Unfortunately, these changes in the proportions of different T cell sub-sets can not be linked to alterations in immune function since HE affected none of these functions. (This abstract does not does not reflect EPA policy. Supported in part by the American Chemistry Council, CRADA 0215-02.)