Acute electric field downregulates human plasma immunoreactive interleukin-6 and -1β levels: Molecular mechanisms underlying inflammation alleviation through electric field therapy

Medical treatment using high-voltage electric potential (HELP) devices to generate an electric field (EF) is an alternative therapy commonly used in Japan. However, the mechanisms underlying potential health benefits of this therapy are still unclear. Therefore, we investigated the effect of HELP exposure (9 kV/electrode+9 kV/ electrode, 30 min) on several cytokines and hormones using enzyme-linked immunosorbent assays in plasma samples obtained from healthy human subjects before and after a single treatment session. Immunoreactive interleukin (IL)-1β and IL-6 levels were significantly downregulated following HELP exposure. Under these treatment conditions, HELP exposure did not exert on immunoreactive IL-10, IL-18, transforming growth factor-beta 1 (TGF-β1), tumor necrosis factor-alpha (TNF-α) adrenaline, serotonin, histamine, neuropeptide Y, somatostatin, insulin, or dehydroepiandrosterone sulfate (DHEAS) levels. The activation of transient receptor potential melastatin 8 (TRPM8) induces the suppression of the levels of inflammatory markers. Therefore, we further examined the in silico docking simulation of lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6 with TRPM8 using a homology model. The binding energies were -10.8, -10.4, and -11.4 kcal/mol for lysoPC-22:4, lysoPE-20:4, and lysoPE-22:6, respectively. Our findings provide new insights into the molecular mechanisms underlying pain control and sleep quality alleviation following EF therapy. Abbreviations: CRP: C-reactive protein; DHEAS: dehydroepiandrosterone sulfate; EF: electric field; HELP: high-voltage electric potential; HODE: hydroxyoctadecadienoic acid; IL: interleukin; lysoPC: lysophosphatidylcholine; lysoPC-22:4: (2-{[(2R)-3-[(7Z,10Z,13Z,16Z)docosa-7,10,13,16-tetraenoyloxy]-2-hydropropyl phosphonato]oxy} ethyl)trimethylazanium; lysoPE: lysophosphatidylethanolamine; lysoPE-22:6: (2-aminoethoxy)[(2R)-2-[(4Z, 7Z, 10Z, 13Z, 16Z, 19Z)docosa-4,7,10,13,16-hexaenoyloxy]-3-hydroxypropoxy]phosphinic acid; lysoPE-20:4: (2-aminoethoxy) [(2R)-2-hydroxy-3-[(5Z, 8Z, 11Z, 14Z)-icosa-5,8,11,14-tetraenoyloxy] propoxy] phosphinic acid; OEA: Oleoylethanolamide; TGF-β: transforming growth factor beta; TNF-α: tumor necrosis factor alpha; TRPM8: transient receptor potential melastatin 8; TRPV1: transient receptor potential vanilloid 1.