title: Influence of phthalates on in vitro innate and adaptive immune responses.
abstract: 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 di-ethyl, 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-γ 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.
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Juliana Frohnert
authors.initials: JF
authors.lastname: Hansen
authors.affiliation: Institute for Inflammation Research, Section 7521, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Claus Henrik
authors.initials: CH
authors.lastname: Nielsen
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marianne Møller
authors.initials: MM
authors.lastname: Brorson
authors.affiliation: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Frederiksen
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Hartoft-Nielsen
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Åse Krogh
authors.initials: ÅK
authors.lastname: Rasmussen
authors.affiliation: Institute for Inflammation Research, Section 7521, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.affiliation: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulla
authors.initials: U
authors.lastname: Feldt-Rasmussen
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D010795:Phthalic Acids / Q000494:pharmacology*; D010835:Phytohemagglutinins; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D010795:Phthalic Acids; D010835:Phytohemagglutinins; C028784:phytohemagglutinin-P; D003993:Dibutyl Phthalate; C007379:diethyl phthalate; C028577:monobutyl phthalate