In vitro effects of nickel (II) and copper (II) complexes with 2,5-bis(2-pyridyl)-1,3,4-thiadiazole on T lymphocyte proliferation and intracellular redox status

Abstract

This work focused on the study of the in vitro effects of different concentrations of copper and nickel complexes of 2,5-bis(2-pyridyl)-1,3,4-thiadiazole on the proliferative responses of human mitogen-stimulated lymphocytes, the Th1-(IL-2, INFγ) and Th2-(IL-4) cytokine secretion and the intracellular oxidant/antioxidant status. The results showed that the ligand (1) and its copper (2) and nickel (3) complexes significantly reduced lymphocyte proliferation in a dose-dependent manner. 1 and 3 decreased IL-2, INFγ and IL-4 secretion with a shift away to Th1 phenotype. 2 reduced IL-2 and INFγ with a shift away to Th2 phenotype. Modulation of immune response was accompanied by an intracellular oxidative stress. Metal complexes have stronger immunomodulating action than their ligand. Nickel was more potent than copper for inhibiting the lymphocyte proliferation and for inducing intracellular oxidative stress, while copper was more potent than nickel for activity against oxidative stress. 2,5-bis(2-pyridyl)-1,3,4-thiadiazole copper and nickel complexes could be of use as a therapy for disorders that involve an inappropriately activated immune response.