Inflammatory response following in vitro exposure to methylmercury with and without n-3 long chain polyunsaturated fatty acids in peripheral blood mononuclear cells from systemic lupus erythematosus patients compared to healthy controls

• Published in: Toxicology in vitro 2018-10, Vol.52, p.272-278
• Main Authors: Crowe, William, Allsopp, Philip J., Nyland, Jennifer F., Magee, Pamela J., Strain, J.J., Doherty, Leanne C., Watson, Gene E., Ball, Elisabeth, Riddell, Claire, Armstrong, David J., Penta, Kayla, Todd, Joshua J., Spence, Toni, McSorley, Emeir M.
• Format: Article
• Language: English
• Subjects: Autoimmune diseases; Chains; Chronic conditions; Cytokines; Dimethylmercury; Docosahexaenoic acid; Eicosapentaenoic acid; Exposure; Fatty acids; Inflammation; Inflammatory diseases; Inflammatory response; Interleukin 8; Leukocytes (mononuclear); Lupus; Mercury; Mercury (metal); Methylmercury; Patients; Peripheral blood mononuclear cells; Polyunsaturated fatty acids; Systemic lupus erythematosus; Tumor necrosis factor-α
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2018.05.008

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. •MeHg provokes a greater inflammatory effect in lupus patients than in controls.•N-3 LCPUFA may mitigate the inflammatory inducing effects of MeHg.•SLE patients should choose varieties of fish low in MeHg and high in n-3 LCPUFA