Effects of tetrabromobisphenol A, a brominated flame retardant, on the immune response to respiratory syncytial virus infection in mice

Abstract

Effects of the brominated flame retardants (BFRs), decabrominated diphenyl ether (DBDE), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), on host immunity of mice were evaluated using respiratory syncytial virus (RSV) infection. Five-week-old female mice were fed a diet containing 1% BFRs for 28days, and subsequently infected with RSV. No toxicological sign was observed in BFR-treated mice before infection. TBBPA significantly increased the pulmonary viral titer in the infected mice on day 5 post-infection, but DBDE and HBCD did not. Slight histological changes were observed in lung tissues of TBBPA-treated mice with mock infection. These changes due to TBBPA were much exacerbated by RSV infection. Cytokine analysis of bronchoalveolar lavage fluid (BALF) from RSV-infected mice treated with or without TBBPA revealed that TBBPA significantly increased the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and interferon (IFN)-gamma at each time point after virus infection, but no change was observed for IL-1beta and IL-12. The levels of IL-4 and IL-10, Th2 cytokines, significantly decreased. Thus, TBBPA caused unusual production of the various cytokines in RSV-infected mice. Flow cytometry revealed that the percentage of double-positive CD4+CD8+ cells, immature T lymphocytes, in the cell populations in BALF from RSV-infected mice increased due to TBBPA treatment. The change was not observed in spleen cells of TBBPA-treated mice. The response to RSV infection verified that TBBPA treatment affected the host immunity of mice. Irregular changes in cytokine production and immune cell populations due to TBBPA treatment were suggested to cause exacerbation of pneumonia in RSV-infected mice.