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 96h with phytohemagglutinin (PHA) and varying concentrations of chlorpropamide and FBP. They were stimulated for 24h with lipopolysaccharide (LPS) and varying concentrations of chlorpropamide and FBP were used. Chlorpropamide at concentrations between 2.5 and 10mM and FBP at concentrations between 1.25 and 10mM decreased proliferation of T-lymphocytes. The chlorpropamide reduced the viability only at a concentration of 10mM and FBP at concentrations of 5.0 and 10mM. The levels of sTNFRII were reduced at chlorpropamide concentrations between 2.5 and 5mM and FBP between 1.25 and 2.5mM. 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.
Subject(s)
Chlorpropamide/adverse effects , Fructosediphosphates/adverse effects , Immunologic Factors/pharmacology , Receptors, Tumor Necrosis Factor, Type II/antagonists & inhibitors , Receptors, Tumor Necrosis Factor, Type II/drug effects , Cell Survival/drug effects , Cell Survival/immunology , Chlorpropamide/immunology , Dose-Response Relationship, Drug , Fructosediphosphates/immunology , Humans , Leukocytes, Mononuclear/cytology , Leukocytes, Mononuclear/drug effects , Lymphocyte Activation/drug effects , Lymphocyte Activation/immunology , Phytohemagglutinins/immunology , Phytohemagglutinins/pharmacology , Receptors, Tumor Necrosis Factor, Type II/chemistry , Shock, Septic/drug therapy , Shock, Septic/immunology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Time FactorsABSTRACT
As alterções celulares e sistêmicas durante a sepse ocasionam distúrbios na circulação, queda na perfuração tecidual e consequentemente déficit de energia celular. A frutose-1-6-bisfosfato (FBP) tem demonstrado efeitos protetores em diversas situações patológicas, inclusive sepse. O objetivo deste travalho foi verificar a concentração de FBP em animais com sepse experimental. Estudo controlado em ratos Wistar divididos em 4 grupos: grupo controle com FBP(500 mg/kg). A concentração sérica de lactato aumentou signitivamente no grupo séptico. Analisando a depuração de creatinina endógena(DCE) verificou-se, que somente o grupo séptico apresentou uma diminuição significativa. Já o lactato urinário não demonstrou alterações entre os grupos de controle, séptico e séptico tratado, aumentando, porém significativamente no grupo co FBP. Este estudo demonstrou que o lactato urinário é bom marcador de perfusão tecidual na spse. Também pôde-se verificar que a ação protetora da FBP não é por melhora da perfusão tecidual, mas provavelmente por outros efeitos já descritos, tais como, ação antiflamatória, manutenção dos níveis de energia da célula, estabilização da membrana celular.
