Immunomodulatory Effects of Copper Bis-Glycinate In Vitro

Copper functions as a cofactor and antioxidants in a large number of enzymes that are important for cellular respiration and the nervous system. In the last century scholars have explored copper's relationship with the immune system, with copper deficiency drastically upsetting the overall function of the immune system, as seen in symptoms such as increased susceptibility to pathogens, decreased proliferation of lymphocytes, and impaired function of both cytotoxic T lymphocytes and helper T cells. Among copper's various forms, copper bis-glycinate (Cbg) has been used as an official EU-approved oral supplement to promote health. In this study, we observed the influence of Cbg on human epithelial cells (HCE-T cells) to determine its cytotoxicity, anti-reactive oxygen (ROS), and wound healing capabilities. We also evaluated Cbg's anti-inflammatory immune cells like primary human mononuclear cells (PBMCs), monocytic THP-1, and Jurkat cells in the context of anti-inflammation. At all the investigated concentrations of Cbg (0.05-100 μg/mL), ther was no considerable impact detected on the epithelial cells. However, the proliferation rate of stimulated PBMCs was affected progressively (3-50 μg/mL). In CD4⁺ helper T cells, interleukin (IL)-17 and IL-2 cytokine levels were decreased in a dose-dependent manner, while interferon (IFN)-γ and IL-2 levels were slightly decreased with no noticeable changes between each treated concentration. Furthermore, stimulated monocytic THP-1 cells treated with Cbg reduced IL-6 and significantly reduced tumor necrosis factor (TNF)-α cytokines secretion. Lastly, stimulated Jurkat intracellular Ca²⁺ influx was significantly inhibited in a dose-dependent manner. Taken together, this study demonstrated that copper possesses modulatory effects on immune cells but not on epithelial cells, but further studies are needed to underline this hypothesis.