In vitro evaluation of the effects of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on IL‐2 production in human T‐cells

Abstract

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 μg ml−1 PFOS or 0, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, or 10 μg ml−1 PFOA. Jurkat cells stimulated with PHA/PMA or anti CD-3 exhibited decreased IL-2 production beginning at 50 μg PFOS ml−1 and 5 μg 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 μg 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.

Perfluorooctanoic acid disrupts gap junction intercellular communication and induces reactive oxygen species formation and apoptosis in mouse ovaries

“…PFOS exposure affected acini maturation but no visible impact on development for acini exposed to PFOA . In a similar way, PFOA did not impact IL‐2 production in human T‐cells, 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 . These studies along with the present study indicate that PFOS has a higher cytotoxic effect on somatic and germ cells than PFOA, which would question the use of PFOS in the fabrication of industrial and consumer products.…”

Immunotoxic and hepatotoxic effects of perfluoro-n-decanoic acid (PFDA) on female Harlan Sprague–Dawley rats and B6C3F1/N mice when administered by oral gavage for 28 days

“…However, PFOA and PFOS also induced gene expression changes that were independent of PPARa for xenobiotic and fatty acid metabolism, inflammation, and cell cycle regulation in PPARa null mice (Rosen et al , 2010. Exposure to PFOA suppressed the T-cell dependent antigen response to SRBC in both PPARa knockout and wild-type C57BL/6 mice (DeWitt et al 2016), while PFOS inhibited IL-2 production in stimulated human Jurkat T-cells in the presence and absence of the PPARa-antagonist GW6471 (Midgett et al 2015), and inhibited TNFa and IL-8 secretion in stimulated THP-1 cells (pro-myelocytic cell line) in the presence and absence of PPARa siRNA (Corsini et al 2011). In vitro, PFDA exposure decreased secretion of TNFa and IL-6 in stimulated human peripheral blood leukocytes (hPBL) and in THP-1 cells, decreased secretion of interferon (IFN)-c by stimulated hPBL, and inhibited NF-jB activation in stimulated THP-1 cells.…”

“…PFOS was consistently the more potent and immunotoxic of the two compounds when directly compared in in vitro studies (Corsini et al 2011(Corsini et al , 2012. Differences in effects on cytokine excretion (Corsini et al 2011;Midgett et al 2015), PPARa activation (Corsini et al 2011), and enhancement/suppression of immune cell populations (Qazi et al 2009(Qazi et al , 2010, suggested different modes of action for the two compounds (Corsini et al 2011). The lack of effect on functional immune Table 5.…”

Environmental perfluorooctane sulfonate exposure drives T cell activation in bottlenose dolphins

“…Yet, reports describing the effects of PFOS on leukocyte proliferation and apoptosis across species remain inconclusive. Whereas oral PFOS exposure resulted in a decreased cell count in the spleens and lymph nodes of mice (Dong et al ., ), exposure of human CD4 + T cells to PFOS in vitro failed to elicit cell death (Midgett et al ., ). Additionally, we have found that treatment of bulk dolphin PBLs with PFOS in vitro further enhanced mitogen‐activated T‐ and B‐cell proliferation, with B cells showing statistical association (Wirth et al ., ).…”