茯苓素诱生肿瘤坏死因子的作用

本文报道茯苓素在小鼠体内，外诱生肿瘤坏死因子的作用。实验表明：茯苓在小鼠体内，外能明显增强经ＢＣＧ预先激活的巨噬细胞产生ＴＮＦ的能力。且有显著的剂量依赖性关系。茯苓素在体内对小鼠移植性肿瘤Ｓ－１８０细胞有明显的抑制生长作用，其作用强弱与ＴＮＦ的水平呈正相关，诱生出ＴＮＦ可通过抗体中和实验得到确证。     

茯苓素体内诱生肿瘤坏死因子（TNF）的机制

茯苓素在小鼠体内诱生肿瘤坏死因子的机制在于增强ＴＮＦ基因的转录。实验结果表明：茯苓素以２７－８１ｍｇ／ｋ剂量刺激小鼠巨噬细胞，可得到较高效率的ｍＲＮＡ表达，超过此剂量可由于药物的毒性作用而造成基因转录水平的下降。     

肿瘤坏死因子的制备及实验观察

肿瘤坏死因子（ＴＮＦ）是一种具有广泛生物活性的细胞因子，它能引起肿瘤广泛出血性坏死，具有抗肿瘤的作用。目前除使用小鼠诱发ＴＮＦ外［１］，也有用家兔进行诱生的［２］。近年随着基因重组技术的发展，基因重组ＴＮＦ的制品也相继诞生［３］。但由于基因重组技术难...     

苦参碱对脂多糖／痤疮丙酸杆菌诱导的小鼠肝炎及产生肿瘤坏死因子的影响

用小鼠致死性肝炎模型和ＴＮＦ体外诱生的方法，研究苦参碱（Ｍａｔ）对脂多糖（ｌｉｐｏｐｏｌｙｓａｃｃｈａｒｉｄｅｓ，ＬＰＳ）诱导的经痤疮丙酸杆菌（ｐｒｏｐｉｏｎｉｂａｃｔｅｒｉｔｔｍａｃｎｅｓ，ＰＡ）预刺激的小鼠产生肿瘤坏死因子（ＴＮＦ）以及致死性肝炎的影响。结果表明：Ｍａｔ（１０，５０ｍｇ·ｋｇ￣（－１），ｉｐ，ｂｉｄ×３ｄ）可降低血清ＴＮＦ和ＡＬＴ水平及小鼠对ＬＰＳ致死毒性的敏感性，并可在体外抑制ＬＰＳ诱导的经ＰＡ预刺激的小鼠腹腔巨噬细胞释放ＴＮＦ。提示Ｍａｔ的保肝作用与其抑制ＴＮＦ释放有关。     

将TNF—α基因导入效应细胞和肿瘤细胞的癌免疫疗法

本文报道了将肿瘤坏死因子（ＴＮＦ）基因导入癌患者的肿瘤浸润淋巴细胞（ＲＩＬ）内，研究其体外抗肿瘤效果。将ＴＮＦ－α基因导入甲基胆蒽诱发的小鼠纤维肉瘤细胞（Ｍｅｔｈ Ａ）内，然后植入同系小鼠体内，研究其对肿瘤增殖的抑制作用。     

苦参碱对细菌脂多糖诱导大鼠枯否细胞释放肿瘤坏死因子及白细胞介素-6的影响

目的是研究苦参碱对细菌脂多糖（ｌｉｐｏｐｏｌｙｓａｃｈｒｉｄｅｓ，ＬＰＳ）诱导经卡西霉素（ｃａｌｃｉｍｙｃｉｎ，Ｃａｌ）预激活的大鼠枯否细胞分泌肿瘤坏死因子（ｔｕｍｏｒｎｅｃｒｏｓｉｓｆａｃｔｏｒ，ＴＮＦ）、白细胞介素６（ｉｎｔｅｒｌｅｕｋｉｎ６，ＩＬ６）的影响以及对小鼠体内产生ＴＮＦ和ＩＬ６的影响。结果，苦参碱１２５，２５０及５００ｍｇ·Ｌ－１剂量依赖性抑制大鼠枯否细胞分泌ＴＮＦ和ＩＬ６；苦参碱５０及１００ｍｇ·ｋｇ－１降低小鼠体内ＴＮＦ和ＩＬ６的水平。提示苦参碱的抗炎作用可能与其抑制ＴＮＦ及ＩＬ６的产生有关。     

恶性肿瘤血清TNF-a测定的临床意义

目的　观察肿瘤患者血清ＴＮＦ－ａ的变化及临床意义。方法　应用放射免疫测定法对２０例健康对照者和 ７０例肿瘤患者进行了血清 ＴＮＦ－ａ含量测定。结果　对照组血清 ＴＮＦ－ａ的含量较低,肿瘤患者明显升高（Ｐ＜０．０１）;肿瘤转移和／或复发时无进一步上升,而肿瘤合并胸腹水和恶液质时ＴＮＦ－ａ上升明显。结论　肿瘤患者血清的ＴＮＦ－ａ水平明显高于对照组,随着肿瘤的局部控制及消退,体内ＴＮＦ－ａ含量呈下降趋势。因此,ＴＮＦ－ａ含量的变化对肿瘤患者病情变化及预后的判定,具有一定的参考价值。     

急性心肌梗塞动物模型中肿瘤坏死因子丙二醛循环内皮细胞作用探讨

肿瘤坏死因子（ＴＮＦ）在冠心病中有重要意义，对ＴＮＦ与ＭＤＡ、ＣＥＣ在急性心梗动物模型中作用及相互关系作一观察，通过动物模型急性心梗组（ＡＭＩ），心梗加用ＴＮＦα单克隆抗体组（ＡＴＭ）和对照组（Ｃ组）实验观察，结果为心梗坏死区占左心室的体积百分数ＡＭＩ组显著高于ＡＴＭ组。ＡＭＩ组ＴＮＦ含量显著高于Ｃ组，而ＡＴＭ组在实验中给予ＴＮＦα单克隆抗体，检测结果为０，ＡＭＩ组血浆ＭＤＡ显著高于Ｃ组和ＡＴＭ组。ＡＭＩ组全血中ＣＥＣ含量显著高于Ｃ组和ＡＴＭ组，推测急性心梗中ＴＮＦα含量升高可加重缺血区心肌细胞和血管内皮的进一步损伤，增加脂质氧化而ＴＮＦα单克隆抗体可明显减轻这些作用，故ＴＮＦα特异抗体在ＡＭＩ早期治疗中有一定应用价值     

重组人肿瘤坏死因子α衍生物3a体外对肿瘤细胞的直接细胞毒作用

研究了重组人肿瘤坏死因子ａ衍生物３ａ（ｒｅｃｏｍｂｉｎａｎｔｔｕｍｏｒｎｅｃｒｉｓｆａｃｔｏｒａｌｐｈａｄｅｒｉｖａｔｉｖｅ３ａ，ｒｈ－ＴＮＦαＤ３ａ）对多种肿瘤细胞株的体外直接杀伤作用，结果表明：ｒｈ－ＴＮＦαＤ３ａ在极低浓度下即能在体外对多种肿瘤细胞发挥明显的直接细胞毒作用，其对Ｌ９２９（小鼠成纤维细胞系）Ｅｈｒｌｉｃｈ（小鼠腹水癌细胞）Ｌｅｗｉｓ（小鼠肺癌细胞）ＳＭＭＣ７７２１（人肝细胞癌）     

氯喹,硝基,乙胺嘧啶对巨噬细胞释出TNF的影响

目的：观察３种抗疟药对疟原虫诱导的大鼠腹腔巨噬细胞释放肿瘤坏死因子（ＴＮＦ）的影响。方法：在酶联免疫法检测细胞培养液中ＴＮＦ的含量。结果：感染约氏疟原虫的红细胞可诱导大鼠腹腔巨噬细胞释放ＴＮＦ，１２ｈ时释出时达高峰。氯喹、硝喹明显抑制ＴＮＦ的释放，乙胺嘧啶作用不明显。结果：氯喹、硝喹抑制ＴＮＦ释放可能是其抗疟作用机制之一。     

Cilostazol Decreases Ethanol-Mediated TNFalpha Expression in RAW264.7 Murine Macrophage and in Liver from Binge Drinking Mice

Alcoholic hepatitis is a leading cause of liver failure in which the increased production of tumor necrosis factor α (TNFα) plays a critical role in progression of alcoholic liver disease. In the present study, we investigated the effects of cilostazol, a selective inhibitor of type III phosphodiesterase on ethanol-mediated TNFα production in vitro and in vivo, and the effect of cilostazol was compared with that of pentoxifylline, which is currently used in clinical trial. RAW264.7 murine macrophages were pretreated with ethanol in the presence or absence of cilostazol then, stimulated with lipopolysacchride (LPS). Cilostazol significantly suppressed the level of LPS-stimulated TNFα mRNA and protein with a similar degree to that by pentoxifylline. Cilostazol increased the basal AMP-activated protein kinase (AMPK) activity as well as normalized the decreased AMPK by LPS. AICAR, an AMPK activator and db-cAMP also significantly decreased TNFα production in RAW264.7 cells, but cilostazol did not affect the levels of intracellular cAMP and reactive oxygen species (ROS) production. The in vivo effect of cilostazol was examined using ethanol binge drinking (6 g/kg) mice model. TNFα mRNA and protein decreased in liver from ethanol gavaged mice compared to that from control mice. Pretreatment of mice with cilostazol or pentoxifylline further reduced the TNFα production in liver. These results demonstrated that cilostazol effectively decrease the ethanol-mediated TNFα production both in murine macrophage and in liver from binge drinking mice and AMPK may be responsible for the inhibition of TNFα production by cilostazol.     

Alleviation of experimental septic shock in mice by acidic polysaccharide isolated from the medicinal mushroom Phellinus linteus

This study reports that acidic polysaccharide (PL) isolated from Phellinus linteus alleviated the septic shock induced by high dose lipopolysaccharide (LPS) injection in mice. To examine the origin of this effect, we investigated cytokine production in serum and the expression of MHC II in B cells and macrophages in areas of inflammation. Pretreatment with PL 24 h before LPS administration resulted in a significant inhibition of up to 68% of circulating tumor necrosis factor (TNF)-alpha, a moderate reduction of 45% of interleukine (IL)-12 and 23% of IL-1beta, but no significant reduction in IL-6. In addition, the expression of MHC II in B cells and macrophages was examined. Our results show that LPS-stimulated cytokine release and the level of MHC II can be modulated by in vivo administration of soluble PL in mice. The decrease of IL-1beta, IL-12 and TNF-alpha in sera and the down-modulation of MHC II during septic shock may contribute to the long survival of mice by PL. Administration of PL in vivo decreases IL-2, IFN-gamma and TNF-alpha production in splencotyes and enhances spontaneous cell apoptosis in macrophages and lymphocytes stimulated with LPS in vitro. Thus, part of the anti-inflammatory effects of PL treatment in vivo may result from the enhanced apoptosis of a portion of the activated macrophages and lymphocytes. The ability of PL to significantly reduce the TNF-alpha production indicates the potential of the polysaccharides in possible therapeutic strategies that are based on down-regulation of TNF-alpha.     

海带多糖对小鼠腹腔巨噬细胞的激活作用

本文研究了海带多糖对Ｃ５７ＢＬ／６小鼠腹腔巨噬细胞的激活作用,结果表明,腹腔注射海带多糖能够明显激活小鼠腹腔巨噬细胞,增强其细胞溶解作用。海带多糖激活小鼠腹腔巨噬细胞,在有ＬＰＳ存在的条件下,能在体外分泌肿瘤坏死因子。     

Activity of Enterococcus faecalis (FK-23) preparation as a biological response modifier]

The biological activity of a preparation of heat killed cells of Enterococcus faecalis, FK-23 which was isolated from the feces of a healthy human, was investigated in C3H/He mice. Intraperitoneal injection of the preparation caused an accumulation of neutrophils and macrophages in the peritoneal cavity of the mice 6 h later. As a parameter of the activation of macrophages, the effect of the FK-23 preparation on the production of tumor necrosis factor (TNF) was examined. The mice were given two consecutive intravenous injections of the preparation at a dose of 10 micrograms/mouse and, 3 h later, of 300 micrograms/mouse. The TNF level in the sera reached 99 U/ml in mice 2 h after the second injection. This preparation also stimulated peritoneal macrophages to produce TNF in vitro and increased the capacity of neutrophils to adhere to plastic plates and to release active oxygens, but did not induce blastogenic transformation of lymphocytes. These results suggest that the FK-23 preparation is a biological response modifier (BRM) with various activities on phagocytes similar to a streptococcal antitumor agent, OK432.     

Pharmacologic modulation of TNF production by endotoxin stimulated macrophages: in vitro and in vivo effects of auranofin and other chrysotherapeutic compounds

The gold compounds, auranofin, sodium aurothiomalate, and triethyl gold phosphine have been demonstrated to inhibit various effector functions associated with monocyte-macrophage populations. Incubation of human peripheral blood monocytes and murine peritoneal macrophages with auranofin or triethyl gold phosphine inhibited TNF production in lipopolysaccharide [LPS] stimulated murine peritoneal macrophages. The inhibitory effect of auranofin and triethyl gold phosphine on LPS stimulated monokine production was reversible when these compounds were incubated with macrophage cultures at concentrations between 0.1-0.5 micrograms/ml. These compounds also inhibited both TNF and IL-1 production by human peripheral blood monocytes. Sodium aurothiomalate at these concentrations had no inhibitory effect on TNF or IL-1 production. Auranofin and triethyl gold phosphine also inhibited TNF production in vivo when compounds were administered orally or intraperitoneally 2 hours prior to a lethal dose of endotoxin. Serum TNF levels from Balb/c mice were significantly reduced when animals were predosed with 1-25 mg/kg of auranofin. The data suggest that the inhibition of TNF production by activated macrophages may contribute to the therapeutic role of gold compounds in the management of chronic inflammatory disease.     

Coumarinic derivatives show anti-inflammatory effects on alveolar macrophages, but their anti-elastase activity is essential to reduce lung inflammation in vivo

We have previously demonstrated the potency of coumarinic derivatives to inhibit human leukocyte elastase. Given the anti-inflammatory activities of some coumarins, we investigated the capacity of our coumarinic derivatives to inhibit inflammation and whether their anti-elastase activity was essential for their anti-inflammatory functions. All compounds studied were coumarinic derivatives displaying differential anti-proteinase activity. Coumarinic derivatives 1, 2, and 3 efficiently inhibited human leukocyte elastase in vitro, whereas the coumarinic derivative 4 did not show inhibitory activity. The anti-inflammatory effect of these compounds and a coumarin control, scopoletin, on interleukin-6 (IL-6), tumor necrosis factor (TNF), and macrophage chemotactic protein-1 (MCP-1) release was studied using lipopolysaccharide (LPS)-stimulated alveolar macrophages. The in vivo effect of compound 2, that inhibits elastase, and compound 4, that does not show proteinase inhibition, was investigated using a mouse model of LPS-induced lung inflammation and elastase-induced acute lung injury. All investigated coumarinic derivatives, regardless of their anti-proteinase activity, significantly inhibited IL-6 and TNF production by LPS-stimulated alveolar macrophages. However, only compounds 2, 3, and 4 significantly reduced MCP-1 release. Compound 2 attenuated LPS-induced leukocyte recruitment in bronchoalveolar lavage, whereas no inhibition was observed with compound 4 devoid of elastase inhibitory capacity. Interestingly, MCP-1 level was reduced in bronchoalveolar lavage of compound 4 treated mice, whereas TNF and IL-6 levels were not modulated by coumarins. Furthermore, compound 2, but not 4, reduced elastase induced lung injury. Our data suggest that although coumarinic derivatives have anti-inflammatory properties, their anti-elastase activity is essential to reduce lung inflammation in vivo.     

Effects of florfenicol on early cytokine responses and survival in murine endotoxemia

Some antibacterials have been reported to regulate the host immune and inflammatory responses both in vitro and in vivo. Florfenicol is an antibiotics used in treatment of infection. We investigated the effects of florfenicol on cytokine production by lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro, and the results showed that florfenicol reduced tumor necrosis factor (TNF) and interleukin-6 (IL-6) production but had little effect on interleukin-1beta (IL-1beta) and interleukin IL-10 (IL-10) secretion. This inspired us to further study the effects of florfenicol in vivo. Florfenicol significantly attenuated TNF and IL-6 production in serum from mice challenged with LPS, and in consistent with the results in vitro. In murine model of endotoxemia, mice were prophylactically or therapeutically treated with florfenicol prior to or after LPS challenge. The results showed that florfenicol significantly increased mouse survival. Further studies revealed that florfenicol prevented the LPS-induced nuclear factor-kappaB (NF-kappaB) translocation from cytoplasm into nuclear in RAW 264.7 macrophages. These observations indicate that florfenicol modulates early cytokine responses by blocking NF-kappaB pathway, and thus, increases mouse survival. This effect of the drug may be of potential usefulness in treatment of bacterial shock.     

Tissue influx of neutrophils and monocytes is delayed during development of trovafloxacin‐induced tumor necrosis factor‐dependent liver injury in mice

Idiosyncratic drug‐induced liver injury (iDILI) has a poorly understood pathogenesis. However, iDILI is often associated with inflammatory stress signals in human patients as well as animal models. Tumor necrosis factor (TNF) and neutrophils play a key role in onset of trovafloxacin (TVX)‐induced iDILI, but the exact role of neutrophils and other leukocytes remains to be defined. We therefore set out to study the kinetics of immunological changes during the development of TVX‐induced iDILI in the established murine model of acute liver injury induced by administration of TVX and TNF. Initially, TNF stimulated the appearance of leukocytes, in particular neutrophils, into the liver of TVX‐treated mice, but even more so in control mice treated with the non‐DILI inducing analogue levofloxacin (LVX) or saline as vehicle (Veh). This difference was apparent at 2 hours after TNF administration, but at 4 hours, the relative neutrophil amounts were reduced again in Veh‐ and LVX‐treated mice whereas the amounts in TVX‐treated mice remained at the same increased level as at 2 hours. The influx of monocytes/macrophages, which was unaffected in Veh‐ and LVX‐treated mice was markedly reduced or even absent in TVX‐treated mice. Unlike controls, mice receiving TVX + TNF display severe hepatotoxicity with clear pathology and apoptosis, coagulated hepatic vessels and increased alanine aminotransferase levels and interleukin 6/10 ratios. Findings indicate that TVX delays the acute influx of neutrophils and monocytes/macrophages. Considering their known anti‐inflammatory functions, the disruption of influx of these innate immune cells may hamper the resolution of initial cytotoxic effects of TVX and thus contribute to liver injury development.     

血小板激活因子拮抗剂WEB2086对小鼠腹腔巨噬细胞释放肿瘤坏死因子的影响(英文)

小鼠ip3%TG 4天后取其腹腔巨噬细胞,血小板激活因子拮抗剂WEB 2086对LPS诱导的巨噬细胞释放肿瘤坏死因子(TNF)有显著的抑制作用。时效研究表明,TNF的产生和WEB 2086的抑制作用从LPS刺激后4 h开始,持续到22 h,在16 h时达到高峰。本文还首次采用一种用放线菌素D和NaF处理的L-929细胞测定TNF的新方法,此法与另外3种生物测定方法进行比较的结果显示此法具有更敏感、方便的特点。