Ex Vivo Human Model for Assessing Immunotoxicity of Per- and Polyfluoroalkyl Substances (PFAS)

Two immune stimuli were applied, including lipopolysaccharide (LPS) to trigger innate responses and phytohemagglutinin (PHA) to activate T-cell-mediated adaptive pathways. Multiple endpoints were assessed, including cytokine secretion, T-cell proliferation, and transcriptomic alterations. This study found that several PFAS analogues suppressed cytokine secretion and disrupted T-cell proliferation to varying degrees following PHA activation.

Transcriptomics results suggest decreased immunoglobulin gene expression, consistent with an immunosuppressive phenotype, although additional validation is required. Overall, the human PBMC model proved to be a cost-effective, ethical, and sensitive new approach method (NAM) that aligned well with prior in vivo data.