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

Toxicol In Vitro. 2018 Oct:52:272-278. doi: 10.1016/j.tiv.2018.05.008. Epub 2018 May 17.

Abstract

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.

Keywords: Cytokines; Docosahexaenoic acid; Eicosapentaenoic acid; Inflammation; Mercury; Systemic lupus erythematosus.

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Docosahexaenoic Acids / pharmacology*
  • Eicosapentaenoic Acid / pharmacology*
  • Environmental Pollutants / toxicity*
  • Female
  • Humans
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Methylmercury Compounds / toxicity*
  • Middle Aged

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Environmental Pollutants
  • Methylmercury Compounds
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid