TY - JOUR
T1 - Influence of Phthalates on in vitro Innate and Adaptive Immune Responses
AU - Hansen, Juliana Frohnert
AU - Nielsen, Claus Henrik
AU - Brorson, Marianne Møller
AU - Frederiksen, Hanne
AU - Hartoft-Nielsen, Marie-Louise
AU - Rasmussen, Åse Krogh
AU - Bendtzen, Klaus
AU - Feldt-Rasmussen, Ulla
PY - 2015/6/25
Y1 - 2015/6/25
N2 - Phthalates are a group of endocrine disrupting chemicals, suspected to influence the immune system. The aim of this study was to investigate the influence of phthalates on cytokine secretion from human peripheral blood mononuclear cells. Escherichia coli lipopolysaccharide and phytohemagglutinin-P were used for stimulation of monocytes/macrophages and T cells, respectively. Cells were exposed for 20 to 22 hours to either diethyl, di-n-butyl or mono-n-butyl phthalate at two different concentrations. Both diesters were metabolised to their respective monoester and influenced cytokine secretion from both monocytes/macrophages and T cells in a similar pattern: the secretion of interleukin (IL)-6, IL-10 and the chemokine CXCL8 by monocytes/macrophages was enhanced, while tumour necrosis factor (TNF)-α secretion by monocytes/macrophages was impaired, as was the secretion of IL-2 and IL-4, TNF-α and interferon-β by T cells. The investigated phthalate monoester also influenced cytokine secretion from monocytes/macrophages similar to that of the diesters. In T cells, however, the effect of the monoester was different compared to the diesters. The influence of the phthalates on the cytokine secretion did not seem to be a result of cell death. Thus, results indicate that both human innate and adaptive immunity is influenced in vitro by phthalates, and that phthalates therefore may affect cell differentiation and regenerative and inflammatory processes in vivo.
AB - Phthalates are a group of endocrine disrupting chemicals, suspected to influence the immune system. The aim of this study was to investigate the influence of phthalates on cytokine secretion from human peripheral blood mononuclear cells. Escherichia coli lipopolysaccharide and phytohemagglutinin-P were used for stimulation of monocytes/macrophages and T cells, respectively. Cells were exposed for 20 to 22 hours to either diethyl, di-n-butyl or mono-n-butyl phthalate at two different concentrations. Both diesters were metabolised to their respective monoester and influenced cytokine secretion from both monocytes/macrophages and T cells in a similar pattern: the secretion of interleukin (IL)-6, IL-10 and the chemokine CXCL8 by monocytes/macrophages was enhanced, while tumour necrosis factor (TNF)-α secretion by monocytes/macrophages was impaired, as was the secretion of IL-2 and IL-4, TNF-α and interferon-β by T cells. The investigated phthalate monoester also influenced cytokine secretion from monocytes/macrophages similar to that of the diesters. In T cells, however, the effect of the monoester was different compared to the diesters. The influence of the phthalates on the cytokine secretion did not seem to be a result of cell death. Thus, results indicate that both human innate and adaptive immunity is influenced in vitro by phthalates, and that phthalates therefore may affect cell differentiation and regenerative and inflammatory processes in vivo.
KW - Adaptive Immunity
KW - Cytokines
KW - Dibutyl Phthalate
KW - Female
KW - Humans
KW - Immunity, Innate
KW - Lipopolysaccharides
KW - Macrophages
KW - Male
KW - Monocytes
KW - Phthalic Acids
KW - Phytohemagglutinins
KW - T-Lymphocytes
U2 - 10.1371/journal.pone.0131168
DO - 10.1371/journal.pone.0131168
M3 - Journal article
C2 - 26110840
SN - 1932-6203
VL - 10
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 6
M1 - e0131168
ER -