The maternal immune response is essential for successful pregnancy, promoting immune tolerance to the fetus while maintaining innate and adaptive immunity. Uncontrolled, increased proinflammatory responses are a contributing factor to the pathogenesis of preeclampsia. The Th1/Th2 cytokine shift theory, characterised by bias production of Th2 anti-inflammatory cytokine midgestation, was frequently used to reflect the maternal immune response in pregnancy. This theory is simplistic as it is based on limited information and does not consider the role of other T cell subsets, Th17 and Tregs. A range of maternal peripheral cytokines have been measured in pregnancy cohorts, albeit the changes in individual cytokine concentrations across gestation is not well summarised. Using available data, this review was aimed at summarising changes in individual maternal serum cytokine concentrations throughout healthy pregnancy and evaluating their association with preeclampsia. We report that TNF-α increases as pregnancy progresses, IL-8 decreases in the second trimester, and IL-4 concentrations remain consistent throughout gestation. Lower second trimester IL-10 concentrations may be an early predictor for developing preeclampsia. Proinflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-8, and IL-6) are significantly elevated in preeclampsia. More research is required to determine the usefulness of using cytokines, particularly IL-10, as early biomarkers of pregnancy health.

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Purpose Long-chain polyunsaturated fatty acids (LCPUFA) can be synthesised endogenously from linoleic acid (LA) and α-linolenic acid (ALA) in a pathway involving the fatty acid desaturase (FADS) genes. Endogenous synthesis is inefficient; therefore, dietary intake of preformed LCPUFA from their richest source of fish is preferred. This study investigated the effect of fish consumption on PUFA concentrations in women of childbearing age while stratifying by FADS genotype. The influence of fish consumption on lipid profile, and markers of inflammation and oxidative stress was also examined. Methods Healthy women (n = 49) provided a buccal swab which was analysed for FADS2 genotype (rs3834458; T/deletion). Participants were stratified according to genotype and randomised to an intervention group to receive either no fish (n = 18), 1 portion (n = 14) or 2 portions (n = 17) (140 g per portion) of fish per week for a period of 8 weeks. Serum PUFA was analysed at baseline and post-intervention. Lipid profile, and markers of inflammation and oxidative stress were also analysed. Results Participants consuming 2 portions of fish per week had significantly higher concentrations of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and total n-3 PUFA, and a lower n-6:n-3 ratio compared to those in the no fish or 1 portion per week group (all p < 0.05). Fish consumption did not have a significant effect on biomarkers of oxidative stress, inflammation and lipid profile in the current study. Conclusion Consumption of 2 portions of fish per week has beneficial effects on biological n-3 PUFA concentrations in women of childbearing age; however, no effects on oxidative stress, inflammation or lipid profile were observed. This trial was registered at www.clinicaltrials.gov (NCT03765580), registered December 2018.

Methylmercury (MeHg) is a proposed environmental stimulus in systemic lupus erythematosus (SLE). Humans are primarily exposed to MeHg through fish consumption. Fish are also important sources of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFA). This in vitro study investigated the inflammatory response of isolated peripheral blood mononuclear cells (PBMCs), when exposed to either MeHg alone or with added n-3 LCPUFA, from SLE patients (N = 12) compared to healthy sex matched controls (N = 12). The PBMCs were isolated and exposed to 200 nM of MeHg for 24 h with or without pre-exposure to eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) at a concentration of 100 μM each. Supernatants were analyzed for the inflammatory markers. Following exposure to MeHg mean TNF-α concentrations were significantly higher in SLE patients (2226.01 ± 348.98pg/ml) compared to controls (701.40 ± 680.65 pg/ml) (P = .008). Pre-exposure of cells with MeHg and EPA resulted in a significantly higher concentration of IL-8 in supernatants from SLE patients (2137.83 ± 1559.01 pg/ml) compared to that of the controls (879.26 ± 979.49 pg/ml) (P = .030). EPA and DHA attenuated the pro-inflammatory inducing effects of MeHg in SLE and control cells. In summary, exposure to MeHg stimulated a higher TNF-α response in SLE patients compared with healthy controls; nevertheless the presence of n-3 LCPUFA reduced the overall inflammatory response, albeit to a lesser degree in SLE patients.

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.