Associations of maternal immune response with MeHg exposure at 28 weeks’ gestation in the Seychelles Child Development Study

Abstract

Problem: Maternal methylmercury (MeHg) exposure may be associated with immune response during pregnancy. Method of Study: In the high fish-eating Seychelles Child Development Study Nutrition Cohort 2, we examined the association of maternal MeHg, polyunsaturated fatty acids (PUFA), and immune markers (Th1:Th2; TNF-α, IL-1β, IFN-ϒ, IL-2, IL-4, IL-5, IL-10, MCP-1, TARC, SFlt-1, VEGFD, CRP and IL-6) at 28 weeks gestation. Linear regression examined associations between MeHg exposure and immune markers with and without adjustment for PUFA. Results: In all models, as MeHg concentrations increased the Th1:Th2 ratio, total Th1 and individual Th1 (IL-1β, IL-2, TNF-α) concentrations decreased. MeHg was not associated with total Th2 cytokines but was associated with a decrease in IL-4 and IL-10. MeHg was positively associated with TARC and VEGFD and negatively associated with CRP. There was a significant interaction between MeHg and the n-6:n-3 ratio, with MeHg associated with a larger decrease in Th1:Th2 at higher n-6:n-3 PUFA ratios. The n-3 PUFA were associated with lower CRP, IL-4 and higher IFN-γ. The n-6 PUFA were associated with higher IL-1β, IL-2, TNF-α, IL-4, IL-10, CRP and IL-6. Conclusion: Maternal MeHg was associated with markers of immune function at 28 weeks gestation. A significant interaction between MeHg and the n-6:n-3 ratio on the Th1:Th2 ratio suggests that the n-3 PUFA may mitigate any immunosuppressive associations of MeHg. The n-3 and n-6 PUFA were associated with suppressive and stimulatory immune responses, respectively. Overall, the associations were of small magnitude and further research is required to determine the clinical significance.

Methylmercury and long chain polyunsaturated fatty acids are associated with immune dysregulation in young adults from the Seychelles child development study.

“…A recent examination of the Nutrition Cohort 2 (NC2) from the SCDS found that increasing MeHg was associated with decreasing Th1:Th2 ( McSorley et al, 2018 ). Hg modulation of cytokine and antibody responses may affect an individual’s susceptibility to autoimmune type disease and also significantly alter host-pathogen interactions increasing susceptibility to infectious disease ( Gardner et al, 2010 ).…”

“…In a high fish consuming cohort from the Amazonian region, MeHg exposure was associated with higher IL-6, IFN-γ, IL-4 and IL-17 cytokine concentrations ( Nyland et al, 2011 ), but other studies have observed no association ( Monastero et al, 2017 ). The majority of research to-date has investigated concurrent Hg exposure with one study reporting an inverse association between prenatal MeHg exposure at 28 weeks gestation and immune markers ( McSorley et al, 2018 ).…”

Potential Association between Methylmercury Neurotoxicity and Inflammation

“…Indeed, a cohort study showed a positive correlation between blood MeHg and the blood cytokine ratio of T-helper1 (cell-mediated immunity) to T-helper2 (humoral immunity). 108) In contrast, cytokine levels in cord blood were unaffected by MeHg exposure of the mother. 109) Therefore, the effect of MeHg on cytokine levels may need to be considered separately for adult and fetus.…”