Exposures to the Environmental Contaminants Pentachlorophenol (PCP) and Dichlorodiphenyltrichloroethane (DDT) Increase Production of the Pro-inflammatory cytokine, Interleukin 1-Βeta (IL-1β), in Human Immune Cells

Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT), are organochlorine environmental contaminants found in human blood at very significant levels (as high as 5 µM for PCP and 260 nM for DDT). Cancers of the blood (lymphoma and myeloma) and kidney as well as others have been associated with exposure to these contaminants. Interleukin 1 beta (IL-1β) is a pro-inflammatory cytokine and is involved in stimulating cell proliferation. High levels of IL-1β are associated with inflammatory diseases and tumor progression. Previous studies showed that PCP and DDT at certain concentrations were able to stimulate secretion of IL-1β. This study shows that the increased secretion of IL-1β seen with both contaminants is due to compound-induced increases in production of this cytokine. Increased production began within 6 h of exposure to PCP and continued to increase out to 24 h. DDT-induced stimulation of IL-1β appeared to be maximal after 6 h of exposure and then diminished by 24 h. The increases seen in IL-1β production stimulated by PCP appear to be at least partially due to compound-induced increases in IL-1β mRNA. Although DDT caused increased production of IL-1β, it did not appear to cause consistent increases in its mRNA. PCP-and DDT-induced increases in IL-1β production were dependent primarily on the p38 MAPK pathway. These results indicate that both PCP and DDT are able to increase IL1-β production in a p38 MAPK dependent manner, which may have the potential to influence chronic inflammation

The organochlorine pesticides pentachlorophenol and dichlorodiphenyltrichloroethane increase secretion and production of interleukin 6 by human immune cells

The environmental contaminants pentachlorophenol (PCP) and 4, 4′-dichlorodiphenyltrichloroethane (DDT) are detected in some human blood samples at levels as high as 5 μM (PCP) and 260 nM (DDT). Several cancers are associated with exposures to these contaminants. IL-6 is a pro-inflammatory cytokine that when dysregulated stimulates inflammatory diseases and tumor progression. Immune cells exposed to PCP at 0.05–5 μM and DDT at 0.025–2.5 μM showed increased secretion of IL-6 when the cell preparations contained either T lymphocytes or monocytes. Increased IL-6 secretion was due to PCP and DDT induced cellular production of the cytokine and was dependent on MAP kinase signaling pathways (in the case of PCP). Compound-induced increases in IL-6 production were in part due to increases in either the transcription of and/or stability of its mRNA. Thus, both PCP and DDT have the potential to produce chronic inflammation by stimulating production of IL-6 by immune cells