Immunomodulatory Effects of Dietary Potassium Perfluorooctane Sulfonate (PFOS) Exposure in Adult Sprague-Dawley Rats

Abstract

Perfluorooctanesulfonate (PFOS) is a stable and environmentally persistent metabolic or degradation product of perfluorooctanyl compounds that were manufactured for a variety of industrial and consumer applications. PFOS itself was sold for use as a surfactant. The structurally related contaminants perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), and N-ethyl perfluorooctane sulfonamide (N-EtPFOSA) were shown to suppress immune responses in laboratory rodents. Relatively low doses of PFOS were found to be immunosuppressive in mice. To assess effects of PFOS on the rat immune system at doses known to alter hepatic function, changes in the morphology and function of immune tissues and cells were measured in adult rats exposed to PFOS in their diet for 28 d at levels ranging from 2 to 100 mg PFOS/kg diet (corresponding to approximately 0.14 to 7.58 mg/kg body weight [bw]/d) and compared to those receiving control diet. Body weight reductions were significant in male and female rats exposed to 50 and 100 mg PFOS/kg diet. Liver/body weight was significantly increased in females exposed to 2 mg PFOS/kg diet and in males exposed to 20 mg PFOS/kg diet. Female rats exposed to 100 mg PFOS/kg diet exhibited a significant increase in spleen weight relative to body weight; these changes lacked a histologic correlate and were not observed in males. While thymus weights relative to body weights were not affected, numbers of apoptotic lymphocytes rose in thymus with increasing dietary PFOS. There was a significant dose-related increase in total peripheral blood lymphocyte numbers in female but not male rats. In both genders the percentages of cells within lymphocyte subclasses were altered. There was a significant trend toward increasing T and T-helper (Th) cells and decreasing B cells with higher PFOS dose. Serum total immunoglobulin (Ig) G1 levels were significantly reduced in males exposed to 2 and 20 mg PFOS/kg diet. The ability of male and female rats to mount delayed-type hypersensitivity (DTH) responses to the T-cell-dependent antigen keyhole limpet hemocyanin (KLH) was not altered by PFOS. There was a significant trend toward elevated KLH-specific IgG in serum from male rats exposed to increasing levels of PFOS in diet. Splenic T- and B-cell proliferation in response to ex vivo mitogen exposure was unaffected by exposure to dietary PFOS. In conclusion, changes in immune parameters in rat did not manifest as functional alterations in response to immune challenge with KLH and may be secondary to hepatic-mediated effects of PFOS in this model.

Mechanism of perfluorooctanesulfonate (PFOS)-induced apoptosis in the immunocyte

“…Their results showed that body weight significantly decreased and the immune organs showed considerable atrophy in either the regular or high-fat diet group. However, consistent with our results, Lefebvre et al (2008) measured changes in immune tissues in adult rats exposed to PFOS for 28 days at levels ranging from 2-100 mg PFOS/kg diet (corresponding to ≈0.14-7.58 mg/kg/ day); their results showed that the relative spleen and thymus weights were not significantly altered in male rats. As such, based on the above results, we believe the relative spleen and thymus weights might be affected not only by the PFOS exposure levels but also exposure times and animal species.…”

“…Reports concerning the immunotoxicity of PFOS in vitro and in vivo have appeared in the literature (Keil et al, 2008;Lefebvre et al, 2008;Peden-Adams et al, 2008;Dong et al, 2009;Qazi et al, 2009;Brieger et al, 2011;Mollenhauer et al, 2011;Wang et al, 2011;Zheng et al, 2011;Corsini et al, 2012;Dewitt et al, 2012). However, there is still a lack of understanding of the toxicokinetics and mode(s)/mechanism(s) of immunotoxic action of PFOS.…”

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

“…It is possible that PFOS skews cytokine production in favor of T H 2 cytokines because, as we noted above, others have reported an increase in IgG after PFOS (Lefebvre et al, 2008) or PFOA (Dewitt et al, 2008) exposure in animals immunized with a novel antigen. Although the precise cause of such an increase in IgG synthesis is unknown, Dewitt et al (2008) suggested this may have been due to a rebound of immune function (which has been observed following a period of immunosuppression) rather than a shift in cytokine production per se.…”

“…PedenAdams et al (2008) noted that both serum SRBC-specific IgM and trinitrophenyl (TNP)-specific IgM titers were suppressed in PFOS-exposed adult mice (both sexes) after challenge with corresponding T-dependent or -independent [TNPlipopolysaccharide] antigens. However, Lefebvre et al (2008) reported a significant trend toward elevated keyhole limpet hemocyanin (KLH)-specific (T-dependent) IgM in the serum of female rats and KLH-specific IgG in the serum of male rats exposed to increasing levels of PFOS. These latter studies also noted no significant changes in KLH-specific IgM and IgG 1 titers in the male rats.…”

Immunotoxicity of Perfluorinated Compounds: Recent Developments

“…In contrast, Qazi et al (2010) reported that 28 days of dietary exposure to PFOS did not affect IgM TDAR in B6C3F1 male mice at serum concentrations 8-to 85-fold greater than occupationally exposed humans. Similarly, Lefebvre et al (2008) indicated that when Sprague Dawley rats were given PFOS in their diet for 28 days, IgG TDAR was not statistically suppressed, although they did not measure IgM TDAR. Qazi et al (2010) proposed that the route of administration has a substantial impact on immunomodulation by PFOS and possibly other PFCs.…”