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.
Martin, TJ, Maise, JQ, Gabure, S, Whalen, MM. Exposures to the environmental contaminants pentachlorophenol and dichlorodiphenyltrichloroethane increase production of the proinflammatory cytokine, interleukin-1β, in human immune cells. J Appl Toxicol. 2019; 39: 1132– 1142. https://doi.org/10.1002/jat.3798