The Effect of Hexabromocyclododecane on the Production of Interleukin‐6 by Human Immune Cells

Abstract

Hexabromocyclododecane (HBCD) is a compound that is used as an additive flame retardant for thermal insulation in buildings, but it can also be used in this manner for furniture fabrics and electrical apparatuses. Due to its hydrophobic properties it can leach from products such as treated fabrics and insulating materials and is found in dust particles, soil, and sewage sludge. This environmental contamination has led to its presence and in a number of foods especially fatty seafood, but also nuts and nut butters. HBCD has been detected in human serum samples. Possible routes for this exposure and accumulation of HBCD in human tissue could be due to exposure to HBCD treated products, dust particles, and ingestion of contaminated foods. Interleukin- 6 (IL-6) is produced by a number of different cell types, including human immune cells. It is involved in cell proliferation, differentiation, apoptosis, and bone remodeling. When IL-6 is overproduced it can lead to chronic inflammation. Diseases such as Castleman disease, Crohn's disease, rheumatoid arthritis, juvenile idiopathic arthritis, bone loss, and cardiovascular disease are associated with overproduction of IL-6. HBCD has been shown to increase the secretion of other pro-inflammatory cytokines. We hypothesize that HBCD may also increase production of IL-6. In this study peripheral blood mononuclear cells (PBMCs) were isolated from leukocyte filters and then exposed to HBCD for 24 hours at different concentrations (5-0.05 μM). Production of IL-6 (combination of secreted and intracellular levels) was determined by measuring secreted levels via enzyme linked immunosorbent assay (ELISA) and intracellular levels via Western blot. Increases in production of IL-6 were seen at five or more of the HBCD exposure levels in cells from 5 different donors. The average increase in IL-6 production seen at the 1 µM exposure was 2.4 fold (ranging from 1.2-3.6 fold) while that at 0.1 µM was 2.2 fold (ranging from 1.2-2.8 fold). These results show thatHBCD can induce increases in production of IL-6. Thus, HBCD may have the potential to contribute to inflammation in exposed individuals.