Abstract
Tetrabromobisphenol A (TBBPA) and hexabromocyclododecane (HBCD), flame retardant compounds used in epoxy resin circuit boards and upholstery, contaminate the environment and are found in human serum. Lymphocytes and monocytes are immune cells that, among other functions, secrete pro-inflammatory cytokines such as interleukin (IL)-1β, an important regulator of immune responsiveness and tissue growth and repair. Thus, if its levels are dysregulated, loss of proper immune function and increased invasiveness of tumors could ensue. This study examines whether exposures to varying concentrations (0.05-5.0 μM) of TBBPA and HBCD for 24 h, 48 h and 6 days interfere with the ability of immune cells to secrete IL-1β. The immune cell preparations examined were human natural killer (NK) cells, monocyte-depleted (MD) peripheral blood mononuclear cells (MD-PBMC) and PBMC. Both increased and decreased secretion of IL-1β from all three types of cell preparation were seen with TBBPA exposures and were dependent on concentration and length of exposure. TBBPA induced changes varied considerably from donor to donor. Exposure to HBCD from 0.5-5.0 μM caused increases in IL-1β secretion after all lengths of exposures in all cell preparations. The specific HBCD levels at which increases occurred varied among donors. Examinations of the signaling pathway(s) responsible for the elevated secretion of IL-1β after HBCD exposure were carried out in MD-PBMC cells. Results revealed that MAPK pathways (ERK1/2 and p38) appear to be the targets of HBCD that lead to increased IL-1β secretion from immune cells.