Blood levels of persistent organic pollutants and circulating biomarkers of systemic inflammation in French women: evidence from the E3N-generations cohort

Persistent organic pollutants (POPs) comprise a diverse class of chemicals characterized by environmental persistence, bioaccumulation, and potential toxicity to humans. Immune and inflammatory dysregulation has been proposed as a key pathway underlying their adverse health effects. This study aimed to investigate associations between circulating levels of multiple POPs—organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and per- and polyfluoroalkyl substances (PFAS)—and biomarkers of systemic inflammation, while accounting for complex exposure patterns. We analyzed a cross-sectional sample of 468 women from the French E3N-Generations cohort. Concentrations of 45 POPs and four inflammatory markers (CRP, IL-8, MCP-1, TNF-α) were measured in blood collected in 1994–1999. Logistic regression models were first applied to assess associations between individual POPs and dichotomized biomarkers. Principal component analysis (PCA) was then used to derive exposure profiles, which were subsequently examined in regression models. Several OCPs were positively associated with CRP levels, a finding corroborated by PCA-based analyses. After false discovery rate (FDR) correction, cis-heptachlor epoxide and dieldrin remained significantly associated with elevated CRP. In contrast, multiple PFAS were inversely associated with IL-8 concentrations, both individually and as part of a shared exposure component. Among them, PFDA, PFNA and PFOS showed the most robust associations after FDR correction. Overall, these findings provide further insight into the complex links between mixed POP exposures and inflammatory processes, highlighting the importance of considering both individual compounds and exposure mixtures.