Nunes Fernanda B, Alves-Filho José Carlos F, Alves Bastos Carolina M, Tessele Paola M, Caberlon Eduardo, Moreira Karla B, Ferreira Taísa M, de Oliveira Jarbas R
Departamento de Ciências Fisiológicas, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Pharmacol Res. 2004 May;49(5):449-53. doi: 10.1016/j.phrs.2003.10.015.
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.
炎症细胞因子在脓毒性休克的发病机制中起核心作用，未来的治疗将依赖于干预这些细胞因子的作用。本研究的目的是探讨两种药物，即高能糖酵解途径中间体1,6-二磷酸果糖（FBP）和氯磺丙脲（磺酰脲类）对T淋巴细胞增殖及肿瘤坏死因子可溶性受体（sTNFRII）水平的影响。通过梯度离心从健康人的血液中分离出外周血单个核细胞（PMBCs）。用植物血凝素（PHA）以及不同浓度的氯磺丙脲和FBP刺激T淋巴细胞96小时。用脂多糖（LPS）刺激它们24小时，并使用不同浓度的氯磺丙脲和FBP。浓度在2.5至10mM之间的氯磺丙脲和浓度在1.25至10mM之间的FBP可降低T淋巴细胞的增殖。氯磺丙脲仅在浓度为10mM时降低细胞活力，FBP在浓度为5.0和10mM时降低细胞活力。当氯磺丙脲浓度在2.5至5mM之间且FBP浓度在1.25至2.5mM之间时，sTNFRII水平降低。总之，我们的结果表明，FBP与氯磺丙脲一样，通过阻断钾通道来抑制细胞增殖，从而降低sTNFRII水平。通过这种方式，它起到了强大的免疫调节作用。
