Journal
JOURNAL OF APPLIED TOXICOLOGY
Volume 35, Issue 5, Pages 459-465Publisher
WILEY
DOI: 10.1002/jat.3037
Keywords
PFOS; PFOA; IL-2 production; immunology; ppar-alpha; perfluorinated compounds; cytokine; human T cells; in vitro; immunosuppression
Categories
Funding
- National Institute of Environmental Health Sciences
- National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health [R21 ES017934, P60 AR062755]
- South Carolina Clinical & Translational Research (SCTR) Institute at the Medical University of South Carolina
- NIH/NCRR [UL1 RR029881, TL1 TR000061]
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Perfluorinated compounds, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), have been shown to alter various immune functions suggesting they are immunotoxic. This study assessed the effects of PFOS and PFOA on interleukin (IL)-2 production in the human Jurkat T-cell line and PFOS in healthy human primary T cells. Jurkat cells were stimulated with phytohemagglutinin (PHA)/phorbol myristate acetate (PMA), anti CD-3/anti CD-28, or anti CD-3, and dosed with 0, 0.05, 0.1, 0.5, 1, 5, 10, 50, 75, or 100 mu gml(-1) PFOS or 0, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, or 10 mu gml(-1) PFOA. Jurkat cells stimulated with PHA/PMA or anti CD-3 exhibited decreased IL-2 production beginning at 50 mu g PFOS ml(-1) and 5 mu g PFOS ml(-1) respectively, but stimulation with anti-CD3/anti-CD28 resulted in no changes compared with the control. Addition of the PPAR-alpha antagonist GW6471 to PFOS-dosed cells stimulated with PHA/PMA resulted in decreases in IL-2 production starting at 50 mu g PFOS ml(-1), which suggests PFOS affected T-cell IL-2 production via PPAR-alpha-independent mechanisms. Exposure to PFOA, PFOA+GW6471, or PFOS+PFOA in Jurkat cells resulted in no significant differences in IL-2 production. In vitro dosing studies using healthy primary human CD4+ T cells were consistent with the Jurkat results. These data demonstrated that PFOA did not impact IL-2 production, but PFOS suppressed IL-2 production in both a human cell line and human primary cells at dose levels within the high end of the human exposure range. A decrease in IL-2 production is characteristic of autoimmune diseases such as systemic lupus erythematosus and should be further investigated. Copyright (c) 2014 John Wiley & Sons, Ltd. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), have been shown to alter various immune functions suggesting they are immunotoxic. This study assessed the effects of PFOS and PFOA on interleukin (IL)-2 production in the human Jurkat T-cell line and PFOS in healthy human primary T cells. These data demonstrated that PFOA did not impact IL-2 production, but PFOS significantly suppressed IL-2 production in both cell types at dose levels within the high end of the human exposure range.
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