Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor (TNF) is a cytokine with pleiotropic biological activity. We have undertaken the present study to evaluate a possible ability of peripheral blood cells of healthy subjects and patients with acute monocytic leukemia to produce TNF alpha. We studied 17 leukemia patients and 8 control subjects. Spontaneous production of TNF alpha induced by LPS and Newcastle disease virus (NDV) were determined in blood cell cultures. Leukemic cells released markedly higher level of TNF alpha than control cells cultured in vitro in contrast to control cells producing TNF spontaneously. It seems that leukemic cells can produce TNF in response to very small amount of LPS; however, we cannot exclude that spontaneous TNF may be involved in autocrine regulation of proliferation and differentiation of bone marrow monocyte precursors.
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PMID:[Spontaneous and induced production of tumor necrosis factor (TNF alpha) by peripheral blood leukocytes in patients with acute leukemia type M 4 and M5 according to FAB]. 765 27

AKR/J mice, highly susceptible to spontaneous T cell leukemogenesis, were protected from developing the disease by H-2-compatible allogenic bone marrow transplantation (BMT) and intermittent treatment with interleukin-2(IL-2). Allogeneic BMT from C3H/HeJ mice and treatment with PBS yielded T cell leukemia in chimeras after the same latent period as that observed in normal AKR/J mice. In contrast, IL-2-treated chimeras caused an incidence of only 40% T cell leukemia. The preventing effect of IL-2 on leukemia development was not observed in one-year-treated chimeras, probably due to a lack of continuous antileukemic effects over the long term. Both LAK and NK activities in spleen cells were significantly increased in IL-2-treated chimeras. The cytotoxicity against T cell lymphoma cell line derived from AKR/J also increased in the IL-2-treated chimeras. Similarly, LPS-, PWM-, and IL-2-induced responses were increased in the IL-2-treated chimeras. TNF-alpha secretion from spleen cells also rose after IL-2-administration. IL-1 beta, IFN-gamma, and TNF-alpha mRNA became detectable in spleen cells using the PCR technique. The characteristics of leukemia cells in chimeras with overt leukemia were not directly affected by IL-2 administration. It is suggested that partial inhibition of spontaneous T cell leukemia development in AKR/J mice by allogeneic BMT and IL-2 may be due to the enhancement of graft-versus-leukemia effects. Further study may provide insights into the mechanisms involved in preventing leukemia development after allogenic BMT and IL-2 in AKR/J mice.
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PMID:Antileukemic effect of interleukin-2 on spontaneous development of leukemia after H-2-compatible allogenic bone marrow transplantation in AKR/J mice. 792 84

Endotoxin (lipopolysaccharide [LPS]) stimulates the production of cytokines, which mediate many of the metabolic effects associated with infection. In LPS-sensitive C57B1/6 mice, LPS doses as low as 0.01 micrograms per mouse decreased adipose tissue lipoprotein lipase (LPL) activity by greater than 50%. In LPS-resistant C3H/HeJ mice, which do not produce cytokines in response to LPS, doses of LPS as high as 10 micrograms per mouse did not affect LPL activity in adipose tissue. In muscle of C57Bl/6 mice, LPL activity was decreased by 27% after 10 micrograms of LPS, whereas in C3H/HeJ mice there was no effect. These results indicate that the LPS-induced decrease in both adipose and muscle LPL activity is mediated by cytokines. Tumor necrosis factor (TNF), interleukin (IL)-1, leukemia-inhibiting factor (LIF), interferon alfa, and interferon gamma all decreased adipose tissue LPL activity in intact mice. In skeletal and cardiac muscle, only IL-1 and interferon gamma decreased LPL activity, whereas TNF, LIF, and interferon alfa had no effect. Inhibition of TNF activity blocked the increase in serum triglycerides that is characteristically observed after LPS but did not affect the ability of LPS to decrease adipose tissue LPL activity. Inhibition of IL-1 activity with IL-1 receptor antagonist partially inhibited the increase in serum triglycerides; however, the ability of LPS to decrease LPL activity in either adipose or muscle tissue was not affected. These data indicate that although TNF and IL-1 play a role in mediating the increase in serum triglyceride levels, these cytokines do not play a crucial role in the inhibition of either adipose or muscle LPL activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of endotoxin and cytokines on lipoprotein lipase activity in mice. 794 14

Treatment of the human myelomonocytic U937 and THP1 cell lines for 24 h with 180 mM of the differentiation inducer DMSO, resulted in priming these cells to subsequent LPS-induced cytolysis. The observed cytotoxicity was LPS dose-dependent and characterized by a prolonged lag phase with detectable effects only appearing after 8 h. LPS-induced apoptotic cell death in DMSO-pretreated U937 cells as indicated by the appearance of 200 basepair DNA fragments upon agarose gel electrophoresis of total cellular DNA. Furthermore, DMSO pretreatment potentiated the cells' capacity to produce cytokines, especially TNF, upon LPS stimulation. This endogenously present TNF was metabolized by the cells. These observations suggested that the LPS-induced cytostasis/cytotoxicity was mediated through TNF. Indeed, medium conditioned by LPS-stimulated U937-DMSO cells was found to exert a cytotoxic effect on U937-DMSO cells that was completely neutralized by anti-human TNF antiserum. Such TNF-like activities were not only present in the supernatant but also at the level of the cell membrane of LPS-stimulated U937-DMSO cells. Apart from TNF, other exogenously applied recombinant cytokines (IL1, IL6, IFN gamma, GM-CSF) were not cytotoxic to U937-DMSO cells. Thus, DMSO-pretreated myelomonocytic cells become sensitive to LPS-induced cytotoxicity, which is, at least in part, mediated through endogenous TNF.
Leukemia 1994 Nov
PMID:Polar agents with differentiation-inducing capacity prime myelomonocytic cell lines to lipopolysaccharide-induced cytolysis: the role of endogenous tumor necrosis factor. 796 41

We have assessed the limitations of the polymerase chain reaction (PCR) as a semiquantitative technique for assessing very low level gene expression. Using PCR, the in vivo expression patterns of the cytokines Leukaemia Inhibitory Factor (LIF) and Interleukin 6 (IL-6) in the normal adult mouse, have been examined. We show that both LIF and IL-6 mRNA are constitutively expressed, albeit at extremely low levels, in most tissues. While it is unclear whether this low level of expression is of biological significance, it is possible that it reflects a local mode of action of these potent polyfunctional molecules. Lipopolysaccharide, the bacterial cell wall product responsible for endotoxic shock, when administered in vivo, was capable of inducing the expression of both LIF and IL-6 in all of the tissues examined. In addition, LIF and IL-6 expression was induced in lung tissue by in vitro culturing in serum-free media. This induction of LIF and IL-6, by LPS and culturing, may reflect the role of these molecules as mediators of the acute phase response to tissue damage.
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PMID:Leukaemia inhibitory factor and interleukin 6 are expressed at very low levels in the normal adult mouse and are induced by inflammation. 805 87

We have found that LPS induces the differentiation of an LPS-resistant subline (LR) of rat myelomonocytic leukemia cell line, c-WRT-7, in vivo, which are resistant to the differentiation inducing effects of LPS in vitro. Furthermore, we have found that the differentiation of LR cells induced by LPS is inhibited by superoxide dismutase, which is one of radical scavengers. Accordingly, we have examined the differentiation inducing effects of xanthine oxidase, a potential source of oxygen radicals, on LR cells in vitro and in vivo. Xanthine oxidase induced the differentiation of LR cells into macrophage-like cells in vitro; and superoxide dismutase inhibited the differentiation of LR cells induced by xanthine oxidase both in vitro and in vivo. These results suggest that oxygen radicals are involved in the differentiation inducing effects of LPS.
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PMID:Involvement of oxygen radicals in the differentiation of rat myelomonocytic leukemia cells in vitro and in vivo. 813 87

TNF, a primary mediator of the response to infection, can be injurious to the organism when present in excessive quantities. Circulating soluble TNF receptors (sTNFR) appear to represent a natural mechanism that protects against circulating TNF. Two soluble TNF receptors (sTNFR-P55 and sTNFR-P75) circulate in vivo and are up-regulated in response to endotoxin. In this study, we investigated the kinetics of LPS-induced sTNFR release and the role of the cytokines TNF, leukemia inhibiting factor, IFN-gamma, and IL-1 in this process. The results show that LPS injection results in a rapid increase in levels of both sTNFR. Although sTNFR-P55 decreases after a peak at 30 min, sTNFR-P75 levels show a peak after 4 to 8 h, after which they slowly diminish. Both human TNF and murine TNF are capable of increasing levels of both sTNFR. Blocking circulating TNF by administration of 3 different anti-TNF agents before LPS injection (mAb to murine TNF, sTNFR55-Fc or sTNFR75-Fc) results in a significant increase of sTNFR-P55 levels, whereas only both sTNFR-Fc constructs also significantly increase sTNFR-P75 levels. Although IL-1 receptor antagonist pretreatment before LPS has no effect on TNF or sTNFR levels, leukemia inhibiting factor pretreatment significantly increases sTNFR-P55 levels. Pretreatment with anti IFN-gamma mAb before LPS results in a significant reduction in TNF and sTNFR-P55 levels, but sTNFR-P75 levels are significantly increased. Our data show that both sTNFR can be up-regulated by LPS and TNF. The influence of TNF, leukemia inhibiting factor, IL-1, and IFN-gamma on the kinetics of LPS-induced circulating sTNFR is discussed in the context of the pathophysiology of LPS-induced disease.
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PMID:LPS-induced sTNF-receptor release in vivo in a murine model. Investigation of the role of tumor necrosis factor, IL-1, leukemia inhibiting factor, and IFN-gamma. 822 46

A mouse monoclonal IgG1 antibody, referred to as NI-58, has been produced. In immunofluorescence assay, this antibody reacted with myelomonocytes, EBV-B cells, Burkitt's lymphoma cells, T cell leukemia cells and peripheral blood mononuclear cells, but not with erythroid cells. The surface antigen on U937 cells recognized by NI-58 had a molecular size of 65 kDa as determined by immunoblotting analysis. As a biological function, NI-58 strongly inhibited the homotypic cell adhesion of LPS-stimulated U937 cells. It was found that the antigen defined by NI-58 was distinct from CD54 (intercellular adhesion molecule-1) in it's pattern of cellular expression and molecular weight, suggesting that NI-58 recognizes a new adhesion molecule and inhibits the homotypic cell adhesion of LPS-stimulated U937 cells.
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PMID:[Establishment of monoclonal antibody NI-58 which inhibits homotypic cell adhesion of LPS-stimulated U937 cells]. 831 9

We have investigated the effects of 1,25-dihydroxyvitamin D3 (D3) and/or transforming growth factor (TGF)-beta on one monocytic (U-937) and two human promyelocytic (HL-60 and AML-193) leukemic cell lines. D3 addition induces a partial monocytic maturation of the cell lines, whereas TGF-beta treatment is largely ineffective. Combined treatment with TGF-beta and D3 causes terminal monocytic maturation, as evaluated both by assessment of a large spectrum of membrane Ag and by functional assays. Furthermore, sequential addition of the two inducers showed that pretreatment with TGF-beta 1 followed by incubation with D3, but not vice versa, induces monocytic maturation as effectively as simultaneous treatment with both agents. In liquid culture the proliferative activity of these cell lines is slightly decreased by D3 and virtually unaffected by TGF-beta, whereas combined treatment with D3 and TGF-beta induces a markedly potentiated inhibitory effect. Furthermore, TGF-beta/D3 treatment (but not D3 alone) elicits the expression of membrane CD14, FcRI, FcRII, CD11a, CD11b, CD11c, ICAM-1, and PECAM-1 Ag at a level comparable to that observed on normal human monocytes. It is noteworthy that several of these Ag play an important role in monocyte physiology (e.g., CD14 Ag mediates the binding of bacterial LPS to monocytes). Treatment with both TGF-beta and D3 (but not D3 alone) induces superoxide anions and H2O2 production similar to that of circulating monocytes. In semisolid culture, D3 and TGF-beta alone cause, respectively, a marked and slight loss of cloning efficiency of the cell lines, whereas their combined addition synergistically results in a complete loss of the cloning capacity. These findings suggest a physiologic role for TGF-beta in monocyte maturation. Furthermore, they may pave the way to the design of clinical protocols combining D3 and TGF-beta in the differentiation therapy of acute promyelocytic/myelomonocytic leukemia.
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PMID:Transforming growth factor-beta potentiates vitamin D3-induced terminal monocytic differentiation of human leukemic cell lines. 838 19

Infection with the avirulent Fukaya strain of Toxoplasma gondii induced few inflammatory responses in the brain of C57BL/6 mice. When mice with chronic infection with the Fukaya strain were challenged with murine leukemia virus (MuLV) LP-BM5, which is known to induce a remarkable immunodeficiency in mice, those mice suffered from a severe encephalitis. Infiltration of mononuclear cells was remarkable in both meninges and parenchyma in those mice. Numerous sites of acute focal inflammation were noted in the brain and the presence of tachyzoites and Toxoplasma antigens was demonstrable in those areas by immunoperoxidase staining using rabbit anti-Toxoplasma IgG antibodies. All mice infected with both T. gondii and LP-BM5 MuLV died from 9 to 14 weeks after the virus infection, whereas no mice died in the infection with either T. gondii or the virus alone. Spleen cells from the mice with coinfection failed to respond to both T cell (Con A) and B cell mitogens (LPS) in vitro in contrast to the cells from mice infected with T. gondii alone that responded to those mitogens just as cells from normal mice did. Mice chronically infected with T. gondii and challenged with LP-BM5 MuLV appears to provide a good animal model of toxoplasmic encephalitis which is a major cause of morbidity and mortality in AIDS patients.
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PMID:Toxoplasma gondii: induction of toxoplasmic encephalitis in mice with chronic infection by inoculation of a murine leukemia virus inducing immunodeficiency. 838 26


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