Influence of Phthalates on Cytokine Production in Monocytes and Macrophages: A Systematic Review of Experimental Trials

Abstract

BackgroundPhthalates 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.Strategy and ResultsA 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.ConclusionResults 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.

Critical Review on the Presence of Phthalates in Food and Evidence of Their Biological Impact

“…The study by Greene et al reported that Di-(2-ethylhexyl)phthalate (DEHP) may act directly on Mɸs increasing chemokine and cytokine gene expression altering their responses, and in women may drive alteration of uterine and/or MΦ factors involved in develop of endometriosis [ 149 ]. Studies that have investigated the influence of phthalates on cytokine secretion by primary human peripheral blood mononuclear cells (MNC) and lymphocytes T showed that phthalate diesters influence cellular signal pathways that lead cytokine production, enhancing the secretion of interleukin (IL)-6, IL-10 and the chemokine CXCL8 and impairing release of tumor necrosis factor (TNF)-α, IL-2, IL-4, and interferon-γ [ 150 ], which could hypothetically prime a decreased synthesis of antibodies, albeit impact of phthalates on cytokine expression was nor confirmed in other studies [ 143 , 151 ]. Other immune parameters, such as weight of lymphoid organs, thymus histology, and antibody levels were evaluated and no effects [ 151 ] or immunosuppression were observed [ 152 ].…”

Characterization of Di-n-Butyl Phthalate Phytoremediation by Garden Lettuce (Lactuca sativa L. var. longifolia) through Kinetics and Proteome Analysis

“…Due to its higher production and application figures, PAEs are widely distributed in various environmental samples such as the air [11], freshwater [12,13], sediment [14,15] and soil [5,[16][17][18]. Several studies have reported that PAEs can cause negative health effects in animals [19,20] and humans [21][22][23]. Therefore, the United States Environmental Protection Agency (USEPA) and government agencies in several other countries have categorized six PAEs as priority environmental pollutants and as endocrine-disrupting compounds (EDCs) [10].…”

MicroRNA-145-5p and microRNA-320a encapsulated in endothelial microparticles contribute to the progression of vasculitis in acute Kawasaki Disease

“…During the inflammatory condition, monocytes/macrophages activated by various stimulants can secrete inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-10, and IL-18 20 . To determine whether the 2 miRs encapsulated in EMPs can modulate the expression level of inflammatory cytokines in monocytes/macrophages, we transfected the 2 miRs into the THP-1 monocytes.…”