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

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.

[1]  P. Murdoch,et al.  A study of respiratory infections in the elderly to assess the role of respiratory syncytial virus. , 1983, The Journal of infection.

[2]  B. Graham,et al.  Protective Role of TNF-α in Respiratory Syncytial Virus Infection In Vitro and In Vivo , 1996 .

[3]  C. Hall,et al.  Respiratory syncytial viral infection in infants with congenital heart disease. , 1982, The New England journal of medicine.

[4]  M. Kurokawa,et al.  Effect of interleukin-12 level augmented by Kakkon-to, a herbal medicine, on the early stage of influenza infection in mice. , 2002, Antiviral research.

[5]  P. Gustafsson,et al.  Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. , 2005, American journal of respiratory and critical care medicine.

[6]  D. Sherrill,et al.  Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years , 1999, The Lancet.

[7]  P. Wyde,et al.  Toxicity and antiviral activity of LY253963 against respiratory syncytial and parainfluenza type 3 viruses in tissue culture and in cotton rats. , 1990, Antiviral research.

[8]  P. Openshaw,et al.  Intracellular IFN-gamma expression in natural killer cells precedes lung CD8+ T cell recruitment during respiratory syncytial virus infection. , 1998, The Journal of general virology.

[9]  C. Janeway,et al.  The Immune System in Health and Disease , 2001 .

[10]  M. Perkins,et al.  Primary respiratory syncytial virus infection in mice , 1988, Journal of medical virology.

[11]  E. Mariussen,et al.  A commercial mixture of the brominated flame retardant pentabrominated diphenyl ether (DE-71) induces respiratory burst in human neutrophil granulocytes in vitro. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[12]  L. Birnbaum,et al.  Brominated flame retardants: cause for concern? , 2003, Environmental health perspectives.

[13]  W. Watanabe,et al.  A new assay system for evaluation of developmental immunotoxicity of chemical compounds using respiratory syncytial virus infection to offspring mice. , 2008, Environmental toxicology and pharmacology.

[14]  NTP Toxicology and Carcinogenesis Studies of Decabromodiphenyl Oxide (CAS No. 1163-19-5) In F344/N Rats and B6C3F1 Mice (Feed Studies). , 1986, National Toxicology Program technical report series.

[15]  C. Janeway.  Immunobiology: The Immune System in Health and Disease , 1996 .

[16]  B. Graham,et al.  Protective Role of TNF-alpha in respiratory syncytial virus infection in vitro and in vivo. , 1996, The American journal of the medical sciences.

[17]  W. Watanabe,et al.  Mouse Model of Respiratory Syncytial Virus Infection to Evaluate Antiviral Activity in Vivo , 1999, Antiviral chemistry & chemotherapy.

[18]  L. Canesi,et al.  Effects of the brominated flame retardant tetrabromobisphenol-A (TBBPA) on cell signaling and function of Mytilus hemocytes: involvement of MAP kinases and protein kinase C. , 2005, Aquatic toxicology.

[19]  L. Anderson,et al.  Respiratory synctial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern , 1996, Journal of virology.

[20]  M. Lebowitz,et al.  Risk factors for respiratory syncytial virus-associated lower respiratory illnesses in the first year of life. , 1991, American journal of epidemiology.

[21]  G. Tiegs,et al.  The flame retardants tetrabromobisphenol A and tetrabromobisphenol A-bisallylether suppress the induction of interleukin-2 receptor alpha chain (CD25) in murine splenocytes. , 2003, Toxicology.

[22]  Rika Nakamura,et al.  Effects of Exposure to Decabromodiphenyl Ether on the Development of the Immune System in Rats , 2008 .

[23]  M. Hirose,et al.  Dietary influence on the impact of ethinylestradiol-induced alterations in the endocrine/reproductive system with perinatal maternal exposure. , 2004, Reproductive toxicology.

[24]  J. Sinnott,et al.  Respiratory Syncytial Virus , 1988, Infection Control & Hospital Epidemiology.

[25]  A. Ogata,et al.  Effects of tetrabromobisphenol A, brominated flame retardant, in ICR mice after prenatal and postnatal exposure. , 2006, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[26]  W. Watanabe,et al.  Effects of decabrominated diphenyl ether (DBDE) on developmental immunotoxicity in offspring mice. , 2008, Environmental toxicology and pharmacology.

[27]  J. Blomberg,et al.  Polybrominated diphenyl ether exposure suppresses cytokines important in the defence to coxsackievirus B3 infection in mice. , 2009, Toxicology letters.