Effects of pentachlorophenol and dichlorodiphenyltrichloroethane on secretion of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) from human immune cells

Abstract

Abstract Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are pesticides that have been widely used and significantly contaminate the environment. Both are found in human blood and have been shown to alter the lytic and binding function of human natural killer (NK) cells. Interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are pro-inflammatory cytokines, which regulate immune responsiveness to pathogens and tumors. Their levels require very tight control to prevent loss of immune competence or excessive inflammation. Here, we examined the capacity of PCP and DDT to alter the secretion of these critical pro-inflammatory cytokines from increasingly reconstituted (more complex) preparations of human immune cells which included NK cells, monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCs) (a preparation that is predominantly lymphocytes) and PBMCs (a preparation containing lymphocytes and monocytes). Results indicated that exposure to PCP decreased IFNγ secretion at the highest exposures (2.5 and 5 μM) and increased IFNγ secretion at lower concentrations. These effects were seen irrespective of the complexity of the cell preparation. PCP at 2.5 and 5 μM generally decreased TNFα secretion from NK cells, but had inconsistent effects in MD-PBMCs and PBMCs. Exposure of each of the immune cell preparations to DDT caused increase in IFNγ secretion. DDT (2.5 μM) increased TNFα secretion from MD-PBMCs after either 24 h or 48 h of exposure. The mechanism of PCP-induced increase in IFNγ secretion appears to involve the p38 mitogen activated protein kinase (MAPK) pathway, based on loss of PCP stimulated increase when this pathway was inhibited.