title: Influence of phthalates on cytokine production in monocytes and macrophages: a systematic review of experimental trials.
abstract: BACKGROUND
  Phthalates are a group of endocrine disrupting chemicals suspected to influence the immune system. The aim of this systematic review is to summarise the present knowledge on the influence of phthalates on monocyte and macrophage production and secretion of cytokines, an influence which could affect both pro- and anti-inflammatory abilities of these cells.
  A systematic search was performed in Medline, Embase and Toxline in June 2013, last updated 3rd of August 2014. Criteria used to select studies were described and published beforehand online on Prospero (http://www.crd.york.ac.uk/NIHR_PROSPERO, registration number CRD42013004236). In vivo, ex vivo and in vitro studies investigating the influence of phthalates on cytokine mRNA expression and cytokine secretion in animals and humans were included. A total of 11 reports, containing 12 studies, were found eligible for inclusion. In these, a total of four different phthalate diesters, six primary metabolites (phthalate monoesters) and seven different cytokines were investigated. Though all studies varied greatly in study design and species sources, four out of five studies that investigated di-2-ethylhexyl phthalate found an increased tumour necrosis factor-α secretion/production from monocytes or macrophages. A summary of cytokine measurements was not possible since few studies were comparable in study design and due to insufficient reporting of raw data for most of the included studies.
  
  
  CONCLUSIONS
  Results from this review have suggested that at least one phthalate (di-2-ethylhexyl phthalate) has the ability to enhance tumour necrosis factor-α production/secretion from monocytes/macrophages in vitro, but also observed ex vivo. Influence of other phthalates on other cytokines has only been investigated in few studies. Thus, in vitro studies on primary human monocytes/macrophages as well as more in vivo studies are needed to confirm or dispute these findings.
authors: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Juliana Frohnert
authors: JF
authors: Hansen
authors: Institute for Inflammation Research, section 7521, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Klaus
authors: K
authors: Bendtzen
authors: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Malene
authors: M
authors: Boas
authors: Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Hanne
authors: H
authors: Frederiksen
authors: Institute for Inflammation Research, section 7521, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Claus H
authors: CH
authors: Nielsen
authors: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Åse Krogh
authors: ÅK
authors: Rasmussen
authors: Department of Medical Endocrinology, PE 2132, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors: Ulla
authors: U
authors: Feldt-Rasmussen
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D010795:Phthalic Acids / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D010795:Phthalic Acids; C032279:phthalic acid