Associations of circulating levels of phthalate metabolites with cytokines and acute phase reactants in a Spanish human cohort Requena Méndez, María del Pilar Pérez-Díaz, Celia Mustieles Miralles, Vicente Peinado, Francisco León, Josefa Pérez Carrascosa, Francisco Miguel Frederiksen, Hanne Salcedo Bellido, Inmaculada Barrios Rodríguez, Rocío Arrebola Moreno, Juan Pedro Phthalate Cytokine Adipokine Supplementary data to this article can be found online at https://doi.org/10.1016/j.envres.2022.114470 The associations between human phthalate exposure and the onset of chronic diseases with an immunological component (e.g., metabolic syndrome, cancer) remain unclear, partly due to the uncertainties in the underlying mechanisms. This study investigates cross-sectional associations of the concentrations of 10 phthalate metabolites with 19 cytokines and acute phase proteins in 213 serum samples of Spanish adults. The associations were explored by Spearman's correlation, multivariable linear regression, and weighted quantile sum regression analyses. In the multivariable analyses, levels of plasminogen activator inhibitor (PAI)-1 were positively associated with mono-n-butyl phthalate (fold-change per one IQR increase in phthalate levels, 95% Confidence Interval: 1.65, 1.45–1.88) and mono-iso-butyl phthalate (3.07, 2.39–3.95), mono-ethyl phthalate (2.05, 1.62–2.61), as well as categorized mono-iso-decyl and mono-benzyl phthalates. The same phthalates also were significantly associated with leptin, interleukin (IL)-18 and monocyte chemoattractant protein-1. Moreover, the proinflammatory markers IL-1β, IL-17, IL-8, IL-6, IL-12, tumor necrosis factor, and lipopolysaccharide-binding protein showed positive and negative associations with, respectively, mono-(2-ethyl-hexyl) and mono-methyl phthalates. Finally, phthalate mixtures were positively associated with PAI-1, leptin, IL-18, IL-12, IL-8 and IL-1β. Despite the cross-sectional design limitation, these associations point to relevant subclinical immuno-inflammatory actions of these pollutants, warranting confirmation in future studies. 2024-05-06T10:06:19Z 2024-05-06T10:06:19Z 2022-10-12 journal article P. Requena et al. Environmental Research 216 (2023) 114470 [https://doi.org/10.1016/j.envres.2022.114470] https://hdl.handle.net/10481/91426 10.1016/j.envres.2022.114470 eng http://creativecommons.org/licenses/by-nc/4.0/ open access Atribución-NoComercial 4.0 Internacional Elsevier