Associations of serum perfluoroalkyl acid levels with T-helper cell-specific cytokines in children: By gender and asthma status

Abstract

Perfluoroalkyl acids (PFAAs) are a group of common chemicals that ubiquitously exist in wildlife and humans. Experimental data suggest that they may alter T-lymphocyte functioning in situ by preferentially enhancing the development of T-helper 2 (TH2)- and inhibiting TH1-lymphocyte development and might increase allergic inflammation, but few human studies have been conducted. To evaluate the association between serum PFAAs concentrations and T-lymphocyte-related immunological markers of asthma in children, and further to assess whether gender modified this association, 231 asthmatic children and 225 non-asthmatic control children from Northern Taiwan were recruited into the Genetic and Biomarker study for Childhood Asthma. Serum concentrations of ten PFAAs and levels of TH1 [interferon (IFN)-γ, interleukin (IL)-2] and TH2 (IL-4 and IL-5) cytokines were measured. The results showed that asthmatics had significantly higher serum PFAAs concentrations compared with the healthy controls. When stratified by gender, a greater number of significant associations between PFAAs and asthma outcomes were found in males than in females. Among males, adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFAAs exposure ranged from 2.59 (95% CI: 1.14, 5.87) for the perfluorobutanesulfonate (PFBS) to 4.38 (95% CI: 2.02, 9.50) for perfluorooctanesulfonate (PFOS); and serum PFAAs were associated positively with TH2 cytokines and inversely with TH1 cytokines among male asthmatics. Among females, no significant associations between PFAAs and TH2 cytokines could be detected. In conclusion, increased serum PFAAs levels may promote TH cell dysregulation and alter the availability of key TH1 and TH2 cytokines, ultimately contributing to the development of asthma that may differentially impact males to a greater degree than females. These results have potential relevance in asthma prevention.

Exposure to Perfluorinated Alkyl Substances and Health Outcomes in Children: A Systematic Review of the Epidemiologic Literature

“…In a subset of that population (NHANES 2005–2006) Stein et al, [ 78 ] found similar elevated ORs with wide CIs for PFOA, PFNA and asthma; they also reported elevated ORS with PFOS, but not PFHxS. In another cross-sectional analysis of asthmatic and non-asthmatic children in Taiwan, increasing quartiles of serum PFOA were associated with increasing odds of asthma [ 82 ]. PFOS, PFBS, PFDA, PFHxS, and PFNA were also associated with asthma, for some PFAS the associations were divergent by sex (PFOS only associated with asthma in males) or potentially sex divergent (PFBS had stronger effect in males), while the others had similar effects across sexes [ 82 ].…”

“…In another cross-sectional analysis of asthmatic and non-asthmatic children in Taiwan, increasing quartiles of serum PFOA were associated with increasing odds of asthma [ 82 ]. PFOS, PFBS, PFDA, PFHxS, and PFNA were also associated with asthma, for some PFAS the associations were divergent by sex (PFOS only associated with asthma in males) or potentially sex divergent (PFBS had stronger effect in males), while the others had similar effects across sexes [ 82 ]. In a cohort across Greenland and the Ukraine Smit, et al [ 83 ] reported generally null associations between asthma or wheeze and a factor representing maternal plasma PFAS concentrations.…”

“…Another study in Taiwan examined IgE levels in children with and without asthma, reporting statistically significant p-values for trend with increasing concentrations of serum PFAS (PFOA, PFOS, PFDA, PFDoA, PFNA, and PFTA), though linear changes were not reported [ 79 ]. In a cross-sectional analysis of asthmatic boys, Zhu et al [ 82 ] observed higher levels of IgE, and Th1 and TH2 cytokines, which might have contributed to asthma development, with higher levels of serum PFOS, PFOA, and PFDA.…”

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food

“…Using the same study Zhu et al. () reported some sex specific associations for immunologic markers of asthma but overall these results were unclear.…”

Developmental Exposures to Perfluoroalkyl Substances (PFASs): An Update of Associated Health Outcomes

“…No other associations were reported between PFAS levels and lymphocyte counts. Another investigation in the Taiwanese GBCA reported positive associations between concurrent serum PFAS concentrations and levels of T helper 2 cytokines [interleukin-4 (IL-4) and IL-5] and negative associations with T helper 1 cytokines (interferon- γ and IL-2) [67]. Finally, umbilical cord blood thymic stromal lymphopoietin and interleukin-33 levels were not associated with 1st trimester pregnancy PFASs concentrations [45] in the Canadian MIREC study, whereas transcriptomics profiling of neonatal cord blood identified a set of differentially expressed genes as being associated with both maternal PFASs concentrations and common cold episodes or rubella titers [59] in a Norwegian study.…”