Perfluorinated compounds: emerging POPs with potential immunotoxicity

Abstract

Perfluorinated compounds (PFCs) have been recognized as an important class of environmental contaminants commonly detected in blood samples of both wildlife and humans. These compounds have been in use for more than 60 years as surface treatment chemicals, polymerization aids, and surfactants. They possess a strong carbon-fluorine bond, which leads to their environmental persistence. There is evidence from both epidemiology and laboratory studies that PFCs may be immunotoxic, affecting both cell-mediated and humoral immunity. Reported effects of PFCs include decreased spleen and thymus weights and cellularity, reduced specific antibody production, reduced survival after influenza infection, and altered cytokine production. Immunosuppression is a critical effect associated with exposure to PFCs, as it has been reported to reduce antibody responses to vaccination in children. Mounting evidence suggests that immunotoxicity in experimental animals can occur at serum concentrations below, within, or just above the reported range for highly exposed humans and wildlife. Considering bioaccumulation and exposure to multiple PFCs, the risk of immunotoxicity for humans and wildlife cannot be discounted. This review will discuss current and recently published work exploring the immunomodulatory effects of PFCs in experimental animals and humans.

Keywords: Cytokine; Immunosuppression; PPAR-α receptor; Perfluorinated compounds; Vaccination.

Figure 1

complexity associated with PFC-induced immunomodulation. The toxicity and immunomodulation induced by exposure to PFCs may occur via multiple pathways, and the relative contributions of these pathways and the role of PPARα likely differ among PFCs and animal species. In human leukocytes, PFCs directly inhibit LPS-induced cytokine production. Both inflammatory cytokines as well as adaptive cytokines were affected by PFCs, with PFOA being the least effective. A role of PPARα in PFOA-induced inhibition of cytokine secretion in human cells exposed in vitro was demonstrated. In contrast, the inhibitory effect of PFCs on in vitro cytokine production by human leukocytes occurred independently of PPARα, and involves the inhibition of NF-kB activation. In particular, PFOS, PFBS and PFDA act upstream by inhibiting I-kB degradation, PFOA, PFOSA and fluorotelomer do not interfere with LPS-induced I-kB degradation, suggesting a downstream effect. All PFCs tested inhibited the phosphorylation of p65 at Ser536, which is required for optimal NF-kB dependent gene transcription and can explain the defective cytokine production following PFCs treatment (Corsini et al., 2012). PFBS, perfluorobutane sulfonic acid; PFDA, perfluorodecanoic acid; Fluorotelomer, 1-Decanol, 3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-heptadecafluoro-(8:2 Telomer), RE, responsive elements.