PFOS alters immune response at very low exposure levels

Researchers find that PFOS affects the immune-system responses in lab mice at levels reportedly found in the general human population.

Perfluorinated compounds previously in stain repellents may be affecting the human immune system, according to new research published in Toxicological Sciences (2008, DOI 10.1093/toxsci/kfn059). After studying mice orally exposed to perfluorooctane sulfonate (PFOS) daily for 28 days, a group of researchers observed that the animals’ immune systems were affected at much lower levels than ever reported.

Margie Peden-Adams, with the Department of Medicine/Pediatrics and the Marine Biomedicine and Environmental Science Center at the Medical University of South Carolina, and colleagues exposed adult male and female mice to levels of PFOS similar to those found in the general human population. These environmentally relevant levels have been recently reported in the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey (NHANES) data. NHANES provides a snapshot of the health, nutrition, and contaminant exposure of the U.S. population.

The paper’s findings support the hypothesis “that some people today could be immunocompromised because of PFOS exposure,” says coauthor Jennifer Keller, a researcher with the Hollings Marine Laboratory in Charleston, S.C.

PFOS is no longer being produced. Its manufacturer, 3M, agreed to phase out production by 2002. But it remains a persistent, global contaminant. The accumulation of PFOS and other perfluorinated compounds, such as perfluorooctanoic acid (PFOA), in wildlife and in humans has been well documented. Although several studies have shown immune suppression in response to PFOA, no published experiments until now have studied PFOS’s immune-system effects, Keller says.

Peden-Adams and colleagues exposed B6C3F1 mice to PFOS orally via a tube daily, with a maximal total administered dose (TAD) of 5 milligrams per kilogram (mg/kg). At the end of the trial the animals had no overt signs of toxicity, but the scientists observed immunotoxic responses. Activity by natural killer cells, a particular type of white blood cell that attacks tumor and virally infected cells, significantly increased (by about 2-fold) in the male mice exposed to PFOS. “Until further studies are done, it is not known if this type of modulation of natural killer cells may be helpful,” explains coauthor Deborah Keil, with the University of Nevada Las Vegas.

At the same time, suppression of the plaque-forming cell (PFC) response, an immune-system activity that indicates that antibodies are attacking and destroying an antigen, occurred in both genders at low exposure levels (0.05 and 0.5 mg/kg TAD for males and females, respectively) when compared with the control mice.

More importantly, however, is the finding that T-independent antibody production was suppressed, Peden-Adams says. The ability of the B-cell to make antibody without aid from T-helper cells was affected. Knowing this is critical to determining how PFOS decreases antibody production and what the risk may be to humans and wildlife, Peden-Adams notes.

“Low-level exposure to PFOS may also affect the immune development during pregnancy,” says Keil. This same group of researchers report in a companion article in Toxicological Sciences (2008, DOI 10.1093/toxsci/kfn015) that the PFC response is impaired in adult mice that were only exposed to PFOS prenatally. “As fetal development is a sensitive time period, it is important to examine any long-lasting effects perfluorinated chemicals may cause during this period,” Keil says.

When the immune system is suppressed, adult animals and humans are more susceptible to disease, Keller says. In work published in 2006 (Environ. Sci. Technol. 40, 4943–4948), Kurunthachalam Kannan, with the Department of Environmental Health Sciences at SUNY, the University at Albany, examined the livers of 80 adult female sea otters off the coast of California. He and colleagues found that concentrations of both PFOA and PFOS were significantly higher in the infected animals compared with levels in the healthy sea otters. Further work with mice and fence lizards is also “suggestive of immune suppression by PFOS,” Kannan adds.

How the immune reaction occurs and its mode and mechanisms of action aren’t clear, Kannan and Peden-Adams say. “Mice may be extremely sensitive to peroxisome proliferator-activated receptors-alpha (PPARα) agonists like PFOS,” Peden-Adams says, “and if the mechanism in any way is due to PPARα, then the health impact on humans may not be a big deal.” This is why further research is needed to understand how the changes are occurring.

Bob Luebke, an immunotoxicologist with the U.S. EPA, says the researchers’ results are “particularly compelling because they found significant suppression of antibody production at serum concentrations similar to those reported in humans.” Kannan agrees: “The good thing about the study is that the exposure doses used are relevant and the serum PFOS concentrations measured are within the ranges found in human populations.” —CATHERINE M. COONEY