Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are brominated flame retardant compounds used in a variety of applications including insulation, upholstery, and epoxy resin circuit boards. Interferon gamma (IFNγ) is an inflammatory cytokine produced by activated T and NK cells that regulates immune responsiveness. HBCD and TBBPA are found in human blood and previous studies have shown that they alter the ability of human natural killer (NK) lymphocytes to destroy tumor cells. This study examines whether HBCD and TBBPA affect the secretion of IFNγ from increasingly complex preparations of human immune cells; purified NK cells, monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCs), and PBMCs. Both HBCD and TBBPA were tested at concentrations ranging from 0.05–5 μM. HBCD generally caused increases in IFNγ secretion after 24 h, 48 h, and 6 day exposures in each of the different cell preparations. The specific concentration of HBCD that caused increases as well as the magnitude of the increase varied from donor to donor. In contrast, TBBPA tended to decrease secretion of IFNγ from NK cells, MD-PBMCs and PBMCs. Thus, exposure to these compounds may potentially disrupt the immune regulation mediated by IFNγ. Signaling pathways that have the capacity to regulate IFNγ production (nuclear factor kappa B (NFκB), p44/42, p38, JNK) were examined for their role in the HBCD-induced increases in IFNγ. Results showed that the p44/42 (ERK1/2) MAPK pathway appears to be important in HBCD-induced increases in IFNγ secretion from human immune cells.

Hexabromocyclododecane (HBCD) and Tetrabromobisphenol A (TBBPA) are brominated flame retardant compounds. HBCD is used in polystyrene insulation, accumulates in living organisms and is highly toxic to aquatic organisms. TBBPA is mainly used in plastic, epoxy resin printed circuit board, and other electronic equipment. Interferon gamma (IFNγ) is an inflammatory cytokine that is produced by activated T cells and NK cells and regulates immune responsiveness. HBCD and TBBPA have been found in human blood and previous studies have shown that they alter the ability of human natural killer (NK) lymphocytes to destroy tumor cells. This study examines whether HBCD and TBBPA affect the secretion of IFNγ from human purified NK cells, monocyte‐depleted (MD) human peripheral blood mononuclear cells (PBMCs), and PBMCs. IFNγ secretion was measured by enzyme linked immunosorbent assay (ELISA). Results indicate that exposures of NK cells, MD‐PBMCs and PBMCs to different concentrations of HBCD and TBBPA (ranging from 5‐0.05 µM) for 24h, 48h, and 6 days influence the ability of immune cells to secrete IFNγ. Certain concentrations of HBCD caused increases in IFNγ secretion after 24 and 48 h exposures (all cell preparations). However, TBBPA decreases secretion of IFNγ from NK cells and MD‐PBMCs but at certain concentrations is able to increase secretion of IFNγ from PBMCs. Thus, exposure to these compounds may potentially disrupt the immune regulation mediated by IFNγ. Additional studies were carried out addressing the signaling pathways that may be involved in HBCD‐induced increases in IFNγ secretion.