IL－6和TNF对白血病细胞的调控作用及意义

通过诱导急性白血病肿瘤细胞自分泌白细胞介素６和肿瘤坏死因子，利用急性白血病原代肿瘤细胞和肿瘤细胞系ＨＬ－６０和Ｋ５６２，分别观察了ＩＬ－６和ＴＮＦα对急性白血病细胞的调控作用。结果发现，急性白血病细胞存在着ＩＬ－６和ＴＮＦα的自分泌作用，而ＴＮＦα和ＩＬ－６对白血病细胞则有诱导分化作用；进一步研究发现，ＴＮＦα对急性白血病细胞株还可呈现生长抑制作用；而ＩＬ－６则可表现为生长促进作用。ＩＬ－６和ＴＮＦα对急性白血病细胞的这种凋控在白血病的发病和免疫调控治疗中将有意义。     

急性白血病患者IL—6,TNF—α和sIL—6R含量及其与白血病负荷的？…

应用生物学检测法，ＥＬＩＳＡ法和间接免疫荧光分析了２４例急性白血病患者外周血ＩＬ－６，ｓＩＬ－６Ｒ和ＴＮＦ－α的含量及其与白血病细胞负荷的相关性。结果显示：（１）急性白血病患者外周血ＩＬ－６，ｓＩＬ－６Ｒ及ＴＮＦ－α水平明显升高，其中急性Ｂ淋巴性白血病的ＩＬ－６，ｓＩＬ－６Ｒ急性Ｔ淋巴性白血病的ＴＮＦ－升高尤为明显；（２）Ｂ－ＡＬＬ的ＩＬ－６，ＴＮＦ－α及Ｔ－ＡＬＬ的ＴＮＦ－α水平与白血病细胞负     

TNF-α基因和IL-2基因共转染的肿瘤细胞体内致瘤性和瘤苗效果的观察

为了探讨两种具有协同作用的细胞因子共转染的瘤苗是否具有更好的抗肿瘤作用，我们将ＴＮＦ－α基因和ＩＬ－２基因转染Ｂ１６黑色素瘤细胞，获得同时分泌ＩＬ－２和ＴＮＦ的Ｂ１６细胞克隆株（命名为Ｂ１６－ＩＬ－２＋－ＴＮＦ－α＋细胞），并观察了其体内致瘤性和瘤苗效果。结果发现，Ｂ１６－ＩＬ－２＋－ＴＮＦ－α＋细胞的体内致瘤性显著低于ＴＮＦ－α基因或ＩＬ－２基因单独转染的Ｂ１６细胞；而且，事先接种Ｂ１６－ＩＬ－２＋－ＴＮＦ－α＋细胞的小鼠能抵抗再接种的野生型肿瘤细胞的生长，表明其具有更佳的瘤苗效果。     

抗CD3单抗对再障病人PBMNC分泌TNF－α和IL－6的影响

抗ＣＤ３单抗体外培育再障患者治疗前后（ｎ＝２０）和正常人（ｎ＝２０）的外周血单个核细胞，设ＰＨＡ组、抗ＣＤ３组、ＰＨＡ＋抗ＣＤ３组和空白组，发现：治疗前，６／２４例再障存在ＴＮＦα自发分泌，ＰＨＡ刺激后，再障组ＴＮＦα分泌量显著高于正常人；体外抗ＣＤ３抑制ＴＮＦα的自发分泌和ＰＨＡ的诱导分泌；抗ＣＤ３治疗后，单个核细胞对ＰＨＡ的促分泌作用处于无应答状态；抗ＣＤ３促进ＩＬ－６的分泌。结果表明，再障时ＴＮＦα分泌异常，抑制ＴＮＦα和促进ＩＬ－６分泌可能是抗ＣＤ３重要的治疗机制。     

急性髓细胞白血病血清IL—6,TNF—α水平的变化及意义

急性髓细胞白血病血清ＩＬ－６、ＴＮＦ－α水平的变化及意义马晓星徐军王鲁群杨道理迟翠芳（济南军区总医院免疫科，济南２５００３１）肿瘤坏死因子（ＴＮＦ）和白细胞介素６（ＩＬ－６）具有多种生物学活性。除发挥正常的生理功能外，还参与了某些肿瘤和白血病的发生、...     

微管功能对单核细胞分泌细胞因子的影响

用秋水仙碱阻断微管聚合，可使ＬＰＳ诱导的人单核细胞ＴＮＦ－α减少，ＩＬ－１β明显增加，反之，用Ｔａｘｏｌ阻断微管解聚，则能抑制ＴＮＦ－α及ＩＬ－１β的产生，而对ＩＬ－６的分泌则有明显刺激作用。以上资料提示微管聚合有利于ＩＬ－６的产生，而微管解聚则促进ＩＬ－１β的释放，对于ＴＮＦ－α的合成似科需要微管动态的聚合与解聚。     

胸腺因子D对白血病IL-6和TNF的调控作用

探讨胸腺因子Ｄ（ＴＦＤ）对白血病患者白介素６（ＩＬ－６）和肿瘤坏死因子（ＴＮＦ）的调控作用,以便在白血病治疗中正确使用ＴＦＤ。在白血病化疗同时,加用ＴＦＤ５０ｍｇ＋１０％葡萄糖注射液５００ｍｌ,ＶＤ,ｑｄ×３ｍｏｎ,检测治疗前后ＩＬ－６活性和ＴＮＦ水平。结果：急性淋巴细胞性白血病（ＡＬＬ）和急性非淋巴细胞白血病（ＡＮＬＬ）的ＩＬ－６和ＴＮＦ均比正常对照组高（Ｐ＜０．０１）。化疗加用ＴＦＤ治疗后,ＡＬＬ的ＩＬ－６和ＴＮＦ及ＡＮＬＬ的ＴＮＦ均比治疗前和化疗组显著降低。ＴＦＤ加化疗药物联合应用,可能是白血病的有效治疗方法。     

秋水仙碱对单核细胞产生细胞因子的影响

微管聚合抑制剂秋水仙碱（Ｃｏｌ，１０－５ｍｏｌ／Ｌ）可抑制ＬＰＳ刺激人单核细胞分泌１７ｋＤＴＮＦ－α及膜相关２６ｋＤＴＮＦ－α；与之相反，它却可促进ＩＬ－１β（多为分泌型）的分泌，而对ＩＬ－１α（多为膜相关型）则表现为抑制作用。对于ＩＬ－６，Ｃｏｌ无明显影响。Ｎｏｒｔｈｅｒｎ分析显示，Ｃｏｌ对ＴＮＦ－α及ＩＬ－１βｍＲＮＡ产生亦表现为相反作用，即对前者抑制，对后者促进作用。     

TNF—α诱导分泌型IL—1和膜型IL—1生成的实验研究

本实验应用丙酸杆菌和内毒素引起的肝坏死模型研究了肿瘤坏死因子α（ＴＮＦα），分泌型白细胞介素１（ｓＩＬ－１）和膜型白细胞介素１（ｍＩＬ－１）在肝坏死形成中的相互作用。其结果：①枯否细胞培养上清液中的ＴＮＦα、ｓＩＬ－１和枯否细胞的ｍＩＬ－１活性较对照组明显增高。ＴＮＦα首先增高，随之为ｍＩＬ－１，最后为ｓＩＬ－１。②ＴＮＦα可以诱导ｓＩＬ－１和ｍＩＬ－１生成。③未发现ＩＬ－１诱导ＴＮＦα生成的作用     

细胞因子对HUVEC分泌IL—6的影响

采用多种细胞因子作用于人脐静脉内皮细胞（ＨＵＶＥＣ），测其ＩＬ－６的分泌。结果表明，ＩＦＮ－γ既可单独诱导又可促进ＴＮＦ－α诱导ＨＵＶＥＣ分泌ＩＬ－６。协同诱导的动力学表明，４－ｈ后ＩＬ－６分泌明显提高。ＩＬ－１ｒａ对ＩＬ－１诱导的ＩＬ－６分泌具有抑制作用，而对ＬＰＳ诱导的ＩＬ－６分泌无影响。ＩＬ－１０可单独诱导ＨＵＶＥＣ分泌ＩＬ－６，工协同促进ＩＬ－１诱导的ＨＵＶＥＣ分泌ＩＬ－６。     

Protective role of interleukin 6 in the lipopolysaccharide-galactosamine septic shock model.

C57BL/6J mice given low doses of lipopolysaccharide (LPS) (100 ng per mouse) plus D-galactosamine (8 mg per mouse) die within 24 h following LPS administration. We used this septic shock model to confirm the role of tumor necrosis factor in mortality using a monoclonal antibody to tumor necrosis factor to prevent lethality. Furthermore, we demonstrated that interleukin 6, rather than playing a lethal role, protected mice against death in this septic shock model. Antibody to interleukin 6 did not affect the fatal outcome in this low-LPS-dose model. However, pretreatment with antibody to tumor necrosis factor did protect the mice against death, in a dose-dependent manner. Moreover, mortality was enhanced by pretreatment with antibody to interleukin 6 when tumor necrosis factor was partly limited by anti-tumor necrosis factor treatment. Mortality was significantly reduced by pretreatment with both recombinant interleukin 6 and low doses of antibody to tumor necrosis factor; in the absence of the low dose of antibody to tumor necrosis factor, interleukin 6 alone did not confer any protection. These data demonstrate in vivo antagonistic activities of tumor necrosis factor and interleukin 6 and show that interleukin 6 can play a protective role against death from septic shock.     

Tumor necrosis factor-alpha and interleukin 6 synergistically induce T cell growth

T cells stimulated with phytohemagglutinin are dependent on monocyte-derived helper signals (e.g. interleukin (IL) 6 and IL 1) for their proliferation. In the present study the effect of recombinant tumor necrosis factor alpha (rTNF-alpha) as a helper signal for growth of highly purified peripheral blood human T cells stimulated with phytohemagglutinin was examined. TNF-alpha alone had a weak co-stimulatory effect, while a combination of TNF-alpha and IL 6 provided highly effective synergistic helper signals for T cell proliferation. The effect of TNF-alpha could not be ascribed to secondary induction of IL 1 production. The effect of TNF-alpha on T cell proliferation was also found to be independent of the autocrine T cell growth factors IL 2 and IL 4. This latter points to dissimilarity between IL 1 and TNF-alpha in the mechanism by which each of these two cytokines in combination with IL 6 promotes T cell proliferation. TNF-alpha, IL 6 and IL 1 thus seem to follow different pathways in their function as helper signals in T cell activation.     

The Neuropilin-1 Ligand,Sema3A,Acts as a Tumor Suppressor in the Pathogenesis of Acute Leukemia

Semaphorin-3A (Sema3A) and vascular endothelial growth factor (VEGF165) are ligands of neuropilin-1 (NRP-1 or CD304) and are related to immunoregulation and tumor angiogenesis, respectively. However, possible interactions between NRP-1 and Sema3A and VEGF165 in acute leukemia remain unclear, especially whether Sema3A plays a role in acute leukemia. In this study, both of the proportion of regulatory T cells (Tregs) and their expression of NRP-1 were found to increase in acute leukemia patients compared with healthy controls. In contrast, lower mRNA and plasma levels of Sema3A were detected in the acute leukemia patients. In vitro, the addition of exogenous Sema3A inhibited the expression of NRP-1 on Tregs and it promoted apoptosis of leukemia cells. However, in the presence of anti-Sema3A antibody, the effect of rhSema3A on NRP-1 expression was reversed. These results suggest that Sema3A promotes apoptosis in leukemia cells by inhibiting expression of NRP-1, and thus, represents a tumor suppressor protein with a role in the pathogenesis of acute leukemia. Consequently, NRP-1/Sema3A signaling may represent a novel target for the treatment of acute leukemia and should be further studied. Anat Rec, 302:1127–1135, 2019. © 2018 Wiley Periodicals, Inc.     

Interleukin-6 and its receptor during homeostasis,inflammation, and tumor growth

Summary This review focuses on describing the specific role of interleukin-6 within the network of inflammatory mediators in man. Sites of interleukin-6 synthesis, regulation of its expression, and the biological functions of this molecule are here outlined. The potential role of interleukin-6 as a diagnostic monitor is discussed. Particular attention is paid to experimental evidence that interleukin-6 and its receptor may be involved in the pathogenesis of autocrine tumor growth. A recently proposed therapeutical use of cytotoxic interleukin-6 fusion proteins in order to selectively destroy certain interleukin-6 receptor bearing tumor cells is discussed in the light of the finding, that not only hepatocytes, but also normal peripheral blood monocytes express the interleukin-6 receptor.Abbreviations ACTH Adenocorticotropic hormone - BCDF B-cell differentiation factor - BSF-2 B-cell stimulatory factor 2 - bp base pairs - CAT chloramphenicol acetyltransferase - cDNA complementary deoxyribonucleic acid - cAMP cyclic adenosinmonophosphate - CHX cycloheximid - CRP C-reactive protein - DNA deoxyribonucleic acid - EBV Epstein Barr Virus - FACS fluorescence activated cell sorter - GMCSF granulocyte-monocyte colony stimulating factor - HSF hepatocyte stimulating factor - HGF hybridoma growth factor - IFN 2 interferon beta 2 - IL-1 interleukin-1 - IL-3 interleukin-3 - IL-6 interleukin-6 - IL6R interleukin-6 receptor - kDa kilo-dalton - LPS lipopolysaccharide/endotoxin - M-CSF macrophage colony stimulating factor - mRNA messenger ribonucleic acid - PDGF platelet-derived growth factor - RNA ribonucleic acid - SAC Staphylococchus aureus Cowan I - TNF tumor necrosis factor/cachectin Dedicated to Hedwig     

急性白血病患者IL-6,TNF-α和sIL-6R含量及其与白血病负荷的相关性

应用生物学检则法,ELISA法和间接免疫荧光法分析了24例急性白血病患者外周血IL-6,sIL-6R和TNF-α的含量及其与白血病细胞负荷的相关性.结果显示:(1)急性白血病患者外周血IL-6,sIL-6R及TNF-α水平明显升高,其中急性B淋巴性白血病(B-ALL)的IL-6,sIL-6R及急性T淋巴性白血病(T-ALL)的TNF-α升高尤为明显;(2)B-ALL的IL-6,TNF-α及T-ALL的TNF-α水平与白血病细胞负荷有着较好的正相关性;而sIL-6R水平与白血病细胞负荷则无明显的相关.由此表明不同类型的白血病存在不同的有利于肿瘤细胞生长的生物因子微环境,这些生物因子及其受体的异常表达与白血病的发生发展相关.     

Glomerular tumor necrosis factor and interleukin 1 during acute aminonucleoside nephrosis. An immunohistochemical study

Acute aminonucleoside nephrosis progresses to glomerulosclerosis. The mechanisms for this phenomenon are not entirely known. Our objectives were to identify macrophage (m phi)-derived peptide growth factors (i.e., tumor necrosis factor and interleukin 1), using immunohistochemical means, in glomeruli of rats with acute aminonucleoside nephrosis. Recently, a role for glomerular m phi s has been suggested as one of the possible mechanisms responsible for this transition from acute glomerular injury to glomerulosclerosis. Since peptide growth factors are elaborated by m phi s and produce alterations in mesangial cell proliferation and protein biosynthesis, we investigated whether these cytokines were present in glomeruli during aminonucleoside nephrosis, which has been typically regarded as a nonimmune toxic glomerulopathy. Fourteen days after puromycin aminonucleoside (PA) delivery, nephrotic control rats (PA/control) and nephrotic animals that had been maintained on an essential fatty acid-deficient (EFAD) diet (PA/EFAD) for 8 weeks before PA, manifested cytoplasmic tumor necrosis factor and interleukin 1 within cells located in the glomerular mesangium as detected by immunohistochemical means. Despite equivalent levels of albuminuria and fasting total cholesterol during peak nephrosis, the PA/EFAD rats had significant reductions in the number of tumor necrosis factor-positive glomerular cells (1.8 +/- 0.1 versus 8.5 +/- 0.4, p less than .001) and interleukin 1-positive glomerular cells (1.5 +/- 0.1 versus 7.2 +/- 0.5, p less than .001) in comparison with the PA/control group. These data correlated with a reduction in the number of ED-1-positive cells (i.e. glomerular m phi s) in glomeruli of PA/EFAD animals as compared with PA/control rats (2.2 +/- 0.3 versus 10.9 +/- 1.4, p less than .001), suggesting that m phi-derived peptide growth factors may be important determinants in initiating a pathobiologic sequence culminating in glomerulosclerosis in this model.     

Growth of Chlamydia pneumoniae induces cytokine production and expression of CD14 in a human monocytic cell line.

Chlamydia pneumoniae was able to survive and to multiply in the human monocytic cell line Mono Mac 6. Growth of C. pneumoniae induced production of tumor necrosis factor alpha, interleukin 1beta, and interleukin 6, as well as up-regulation of the CD14 molecule in a time-dependent manner. Infection of monocytic cells and a proinflammatory cytokine response may be important in C. pneumoniae pathogenesis.