Pentachlorophenol and Dichlorodiphenyltrichloroethane alter secretion of interferon gamma (IFNγ) from human immune cells
Pentachlorophenol (PCP) is an organochlorine compound registered for use as an insecticide, fungicide, herbicide, molluscicide, andalgicide. Its usage was limited in 1984 but it is found in human blood at significant levels. Dichlorodiphenyltrichloroethane (DDT) anotherorganochlorine has been used as an agricultural pesticide and to regulate mosquitoes. Even though the USA banned the use of DDT, many countries continue to use DDT and detectable levels are found in human blood samples in the US. Interferon gamma (IFNγ) is an inflammatory cytokine produced by activated T cells and natural killer (NK) cells that regulates immune responsiveness. PCP and DDT have been shown to alter the ability of human NK lymphocytes to destroy tumor cells. This study examines whether PCP and DDT affect the ability of NK cells, monocyte-depleted (MD) human peripheral blood cells (PBMCs), and PBMCs to secrete IFNγ. Exposures of NK cells, MD-PBMCs and PBMCs to PCP (0.05-5 μM) and DDT (0.025-2.5 µM) for 24h, 48h, and 6 days altered the ability of immune cells to secrete IFNγ. Higher concentrations of PCP (5 and 2.5 μM) decreasedIFNγ secretion from all immune cell preparations, while lower concentrations of PCP stimulated secretion. DDT increased secretion of IFNγ from NK cells, MD-PBMCs, and PBMCs at one or more exposure concentration after at least one length of exposure. Thus, exposure to these compounds may potentially disrupt the immune regulation mediated by IFNγ. MD-PBMCs were further studied to determine the mechanism of PCP-induced increases in IFNγ secretion. Mitogen-activated protein kinase (MAPK) and the nuclear factor kappa B (NFκB) pathways were examined for roles in PCP-induced increases in IFNγ secretion. Results showed that MAPK pathways, p44/42 and p38, appear to be targets of PCP which lead to increased IFNγ secretion from human immune cells.
Reda H Massawe,
"Pentachlorophenol and Dichlorodiphenyltrichloroethane alter secretion of interferon gamma (IFNγ) from human immune cells"
ETD Collection for Tennessee State University.