Effect of the chlorpropamide and fructose-1,6-bisphosphate of soluble TNF receptor II levels.
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.
Nunes
Fernanda B
FB
Departamento de Ciências Fisiológicas, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Alves-Filho
José Carlos F
JC
Alves Bastos
Carolina M
CM
Tessele
Paola M
PM
Caberlon
Eduardo
E
Moreira
Karla B
KB
Ferreira
Taísa M
TM
de Oliveira
Jarbas R
JR
D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002747:Chlorpropamide / Q000009:adverse effects* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005635:Fructosediphosphates / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology / Q000494:pharmacology; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000187:drug effects*; D012772:Shock, Septic / Q000188:drug therapy / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D005635:Fructosediphosphates; D007155:Immunologic Factors; D010835:Phytohemagglutinins; D047889:Receptors, Tumor Necrosis Factor, Type II; C029063:fructose-1,6-diphosphate; D002747:Chlorpropamide