A study of the effect of complexes of 3d-metal ions with gluconic acid on synthesis of cytokines in experimental immunodeficiency

Abstract

Aim. Evaluation of the influence of synthesized gluconates of 3d-metals on production of cytokines in blood serum of mice with experimental immunodeficiency.
 Materials and Methods. The effect of complex compounds of bivalent 3d-metals (Mn, Fe, Co, Cu, Zn) with glucuronic acid on production of cytokines: interleukin (IL)-1β, IL-6, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) in blood serum of mice with experimental immunodeficiency induced by a single intraperitoneal administration of cyclophosphamide at the dose of 50 mg/kg was studied. 3d-Metal gluconates (10-2mol/l) were orally introduced for comparison with immunostimulatory drug «Licopid®» and calcium gluconate (doses were calculated according to the instructions) daily for two weeks, starting from the second day after the injection of cyclophosphamide. Levels of cytokines were determined by immunoenzyme analysis.
 Results. On the 16th day after the induction of immunodeficiency, levels of cytokines in blood serum of mice decreased: IL-1β – by 75.0%, IL-6 – by 65.2%, IFN-γ – by 61.6%, TNF-α –by 55.6% (p<0.05). Stimulatory effect of gluconates of 3d-metals on synthesis of cytokines depended on the used metal: the effect of MnGl, FeGl, CoGl, CuGl was lower than of licopid. ZnGl produced a weaker effect than licopid only on synthesis of IL-6, and equal effect on secretion of IL-1β and IFN-γ, and the highest effect on TNF-α (p<0.05 for all comparisons). Calcium gluconate did not produce any significant effect on the content of cytokines.
 Conclusion. The obtained results show a significant role of 3d-metals in maintenance of immune homeostasis, which, taking into account the literature data, may be explained by their action through activation of the nuclear transcription factor NF-κB which controls expression of cytokines.