Effect of the chlorpropamide and Fructose-1,6-bisphosphate on soluble TNF receptor II levels

Abstract

Inflammatory cytokines are central to the pathogenesis of septic shock, and future therapies will depend on interfering with the effects of these cytokines. The aim of this study was to investigate the effect of the two drugs, Fructose-1,6-bisphosphate (FBP), a high-energy glycolytic pathway intermediate, and chlorpropamide (sulfonylurea) on proliferation of T-lymphocytes and on the levels of soluble receptors of tumor necrosis factor (sTNFRII). Peripheral blood mononuclear cells (PMBCs) were isolated from the blood of healthy humans by gradient centrifugation. T-lymphocytes were stimulated for 96 h with phytohemagglutinin (PHA) and varying concentrations of chlorpropamide and FBP. They were stimulated for 24 h with lipopolysaccharide (LPS) and varying concentrations of chlorpropamide and FBP were used. Chlorpropamide at concentrations between 2.5 and 10 mM and FBP at concentrations between 1.25 and 10 mM decreased proliferation of T-lymphocytes. The chlorpropamide reduced the viability only at a concentration of 10 mM and FBP at concentrations of 5.0 and 10 mM. The levels of sTNFRII were reduced at chlorpropamide concentrations between 2.5 and 5 mM and FBP between 1.25 and 2.5 mM. In conclusion, our results suggest that FBP acts, as does chlorpropamide, to inhibit the cellular proliferation and thereby reducing the sTNFRII levels through blockage of the potassium channels. In this way it acts as a powerful immunomodulatory agent.