Pentachlorophenol and Dichlorodiphenyltrichloroethane Effects on the Synthesis of Interleukin 1 Beta and Secretion and Synthesis of Interleukin 6 by Human Immune Cells
Pentachlorophenol (PCP) is an environmental contaminant found in human blood at levels as high as 5 µM. PCP has been used in insecticides, herbicides, and antifouling paint. 4, 4'-Dichlorodiphenyltrichloroethane (4, 4?-DDT), is found in human body fluids as high as 23, 169 ng/g of lipid (approximately 260 nM). Cancers of the blood (lymphoma and myeloma) and kidney as well as others have been associated with exposure to these contaminants. Previous studies in our lab show that PCP and DDT inhibit the lytic function of highly purified human natural killer (NK) lymphocytes and decrease the expression levels of several surface proteins on NK cells. Interleukin 1-beta (IL-1β) is a pro-inflammatory cytokine and is involved in stimulating cell proliferation. Interleukin 6 (IL-6) is a pro- inflammatory cytokine produced by T lymphocytes and macrophages in response to infection. Elevation of both cytokine levels has been associated with inflammatory diseases and tumor progression. Increased levels of IL-1β or Il-6 may lead to immune dysfunction or increased potential for inflammatory disorders and tumors. The objective of this study was to examine if exposure of human immune cells to PCP and DDT alters synthesis of IL1-β and synthesis and secretion of IL-6. Peripheral Blood mononuclear cells (PBMCS), monocyte-depleted (MD) PBMCs, and enriched NK cells were used in this study. Cells were exposed to different concentrations of PCP and DDT for different time periods. Synthesis of IL1-? and IL-6 were measured using ELISA (enzyme-linked immunosorbent assay) western blots, and RT-PCR. Immune cells all showed increased synthesis of IL-1β and IL-6 after at least one length of exposure to at least one concentration of PCP and DDT. Additionally, the PCP-induced increases in IL-1β and IL-6 synthesis were dependent primarily on the p38 MAPK pathway. These results suggest that PCP and DDT induced alterations in IL1-? and IL-6 synthesis may have the potential to cause immune system dysregulation.
Tamara J Martin,
"Pentachlorophenol and Dichlorodiphenyltrichloroethane Effects on the Synthesis of Interleukin 1 Beta and Secretion and Synthesis of Interleukin 6 by Human Immune Cells"
ETD Collection for Tennessee State University.