Immunotoxic effects of dietary toxicants : focus on prenatal exposure to acrylamide, polychlorinated biphenyls and dioxins
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AbstractFood contains toxicants which may exert adverse effects on the immune system. The result can be immune-related diseases such as allergy, asthma and autoimmune conditions, or increased susceptibility to infectious diseases and cancer. The overall aim of the present work was to investigate the immunotoxic potential of dietary toxicants, with focus on prenatal exposure to toxicants from the maternal diet. Prenatal exposure to immunotoxicants is of particular concern since the foetus may be especially vulnerable due to an extensively developing immune system.
To examine whether release of cytokines in an in vitro system can be used as a marker of immunotoxic properties of dietary toxicants, human peripheral blood mononuclear cells were exposed in vitro to 12 dietary toxicants. Both immunotoxic and non-immunotoxic substances, classified according to published in vivo studies, were included. All 12 dietary toxicants affected the release of one or more of the nine cytokines included, and the exposure to each of the toxicants resulted in different cytokine release patterns. Although the effects on the release of each cytokine were examined separately and in combinations of cytokines, the in vitro cytokine release could not be used to differentiate between the immunotoxic and the non-immunotoxic substances.
Of the 12 dietary toxicants, the environmental pollutants polychlorinated biphenyls (PCBs) and dioxins, as well as acrylamide formed during food preparation, were chosen for further examination in a birth cohort. The birth cohort BraMat (n=205), a sub-cohort of the Norwegian Mother and Child Cohort Study (MoBa), was established to investigate whether prenatal exposure to these toxicants from the maternal diet increases the risk of immunerelated diseases in the child. The children were followed using annual questionnaires covering health outcomes during their three first years of life. Immune-related blood parameters were examined at three years of age. The maternal intake of the toxicants during pregnancy was calculated using a validated food frequency questionnaire from MoBa, and the levels were assumed to be representative for the general population. Prenatal dietary exposure to PCBs and dioxins was found to be associated with an increased risk of wheeze (periods of more than 10 days with dry cough, chest ightness or wheeze, or shortness of breath), the childhood disease exanthema subitum and more frequent upper respiratory tract infections during the three first years of life. Further, at three years of age, exposure to PCBs and dioxins was found to be associated with a reduced antibody response to measles vaccine. No associations were found between prenatal exposure to PCBs and dioxins and immunophenotype data including levels of regulatory T cells, allergic sensitization or antibody responses to other vaccines than measles. Prenatal acrylamide exposure was not found to be associated with any of the children’s health outcomes or blood parameters.
In conclusion, the in vitro study, within the limitations of the study design, does not support the replacement of in vivo studies with in vitro cytokine release studies for identification of immunotoxic substances. In the BraMat cohort, prenatal exposure to acrylamide from the maternal diet was not found to be associated with immune-related health outcomes or blood parameters, but the statistical power may be too low to conclude on negative findings. However, prenatal exposure to PCBs and dioxins from the maternal diet may increase the risk of wheeze and the susceptibility to infectious diseases during early childhood. Overall, continued efforts to reduce the exposure to PCBs and dioxins from food for women of fertile age may be beneficial for their children’s health.
List of papers
|Paper I: Stolevik, S.B., Nygaard, U.C., Namork, E., Granum, B., Pellerud, A., van Leeuwen, D.M., Gmuender, H., van Delft, J.H., van Loveren, H., Lovik, M. In vitro cytokine release from human peripheral blood mononuclear cells in the assessment of the immunotoxic potential of chemicals. Toxicol. In Vitro. 2011, 25, 555-562. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1016/j.tiv.2010.11.021|
|Paper II: Stolevik, S.B., Nygaard, U.C., Namork,E., Haugen, M., Kvalem, H.E., Meltzer, H.M., Alexander, J., van Delft, J.H., van Loveren, H., Lovik, M., Granum, B. Prenatal exposure to polychlorinated biphenyls and dioxins is associated with increased risk of wheeze and infections in infants. Food Chem. Toxicol. 2011, 49, 1843-1848. The paper is removed from the thesis in DUO due to publisher restrictions. The published version is available at: https://doi.org/10.1016/j.fct.2011.05.002|
|Paper III: Stolevik, S.B., Nygaard, U.C., Namork, E., Haugen, M., Meltzer, H.M., Alexander, J., Knutsen, H.K., Aaberge, I., Vainio, K., van Loveren, H., Lovik, M., Granum, B. Immunosuppressive effects of prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet persist into early childhood. submitted version, published as: Stølevik SB, Nygaard UC, Namork E, Haugen M, Meltzer HM, Alexander J, Knutsen HK, Aaberge I, Vainio K, van Loveren H, Løvik M, Granum B. Prenatal exposure to polychlorinated biphenyls and dioxins from the maternal diet may be associated with immunosuppressive effects that persist into early childhood. NOTICE: this is the author s version of a work that was accepted for publication in Food Chem Toxicol. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in: Food Chem Toxicol. 2013 Jan;51:165-72. The published version of this paper is available at: https://doi.org/10.1016/j.fct.2012.09.027|