Hexabromocyclododecane and tetrabromobisphenol A alter secretion of interferon gamma (IFN-γ) from human immune cells

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 (IFN-gamma) 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 IFN-gamma 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 to 5 A mu M. HBCD generally caused increases in IFN-gamma 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 IFN-gamma from NK cells, MD-PBMCs, and PBMCs. Thus, exposure to these compounds may potentially disrupt the immune regulation mediated by IFN-gamma. Signaling pathways that have the capacity to regulate IFN-gamma production (nuclear factor kappa B (NF-kappa B), p44/42, p38, JNK) were examined for their role in the HBCD-induced increases in IFN-gamma. Results showed that the p44/42 (ERK1/2) MAPK pathway appears to be important in HBCD-induced increases in IFN-gamma secretion from human immune cells.