The atrophy and changes in the cellular compositions of the thymus and spleen observed in mice subjected to short-term exposure to perfluorooctanesulfonate are high-dose phenomena mediated in part by peroxisome proliferator-activated receptor-alpha (PPARα)

Type 1 and Type 2 cytokines imbalance in adult male C57BL/6 mice following a 7-day oral exposure to perfluorooctanesulfonate (PFOS)

“…Our studies, as well as those of other investigators, have shown that these compounds can activate certain components of innate immunity (Qazi et al, 2009a) but suppress acquired immunity (Yang et al, 2000(Yang et al, , 2001(Yang et al, , 2002aDewitt et al, 2008;Peden-Adams et al, 2008;Dong et al, 2009;Qazi et al, 2009b;Zheng et al, 2009). For instance, 7-10 days of dietary or gavage exposure of mice to either PFOS or perfluorooctanoate (PFOA) causes severe atropy of the thymus (central organ) and spleen (peripheral organ), two important immune organs for acquired immune responses (Yang et al, 2000(Yang et al, , 2001(Yang et al, , 2002aQazi et al, 2009b). At the same time, the populations of splenocytes and thymocytes of all phenotypes are reduced dramatically in size.…”

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

“…Under the daily exposure paradigm, acute toxicity prevented evaluation above 0.5 mg PFDA/kg. Though no adverse effects were observed on functional measures of cell-or humoral-mediated immunity, suppression of immune cell populations in the spleen could be an early indicator of immunosuppression, with impaired function at higher doses or longer exposure periods (Qazi et al 2009). …”

“…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.…”

“…Immune cell phenotype determination in the spleen is a reliable indicator of immunotoxicity in mice, with a concordance rate of 83% (Luster et al 1992;FDA 2002). At 5.0 mg PFDA/kg/week, spleen weight, total spleen cells, the total numbers of Ig þ , NK þ , and B-cells (Qazi et al 2009) in C57BL/6 mice exposed to PFOA or PFOS at subacute toxicity levels, of alterations in the proportions and numbers of T-cells, B-cells, immature T-cells, and phagocytes in spleen and thymus of C57BL/6 mice exposed to 0.1 mmol PFNA/kg (Rockwell et al 2013(Rockwell et al , 2017, and of splenic atrophy following exposure to PFOS (C ¼ 8), PFOA (C ¼ 8), PNFA (C ¼ 9), or PFDA (C ¼ 10) (Harris et al 1989;Qazi et al 2009;Rockwell et al 2013Rockwell et al , 2017. No significant changes were observed in splenic leukocyte sub-populations in PFDA-exposed HSD rats.…”

“…Exposure of laboratory animals to PFOA and PFOS has resulted in hepatomegaly, hepatic peroxisome proliferation, atrophy and alteration of cell populations in lymphoid organs (Yang et al 2000;Qazi et al 2009;Son et al 2009;DeWitt et al 2012;Dong et al 2012), suppression of the T-cell-dependent IgM antibody response (TDAR), alterations in inflammatory cytokine signaling (Peden-Adams et al 2008;Zheng et al 2009Zheng et al , 2011Dong et al 2011;DeWitt et al 2012), and reduction in thyroid hormone levels (Curran et al 2008). PFOS reduced the host resistance to influenza A virus and natural killer cell activity in B 6 C 3 F 1 mice (Guruge et al 2009).…”