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)

Total absence of CSF-1 in the op/op mouse leads to a profound and generalized deficiency of macrophages and to osteopetrosis subsequent to the absence of osteoclasts. These observations confirm that CSF-1 is a genuine regulator of macrophage and osteoclast formation in vivo. Further studies in affected animals have shown that the CSF-1 absence variably affects macrophage differentiation stages and different organ macrophage populations, and that functionally competent macrophages are produced in low numbers without CSF-1, presumably under the influence of GM-CSF and IL-3. The op/op mice have increased levels of both endogenous GM-CSF and IL-3, which apparently are not fully able to compensate for the absence of CSF-1. Macrophage deficiencies but not osteoclast deficiencies in the op/op mouse could be completely corrected by exogenous GM-CSF, while exogenous CSF-1 corrects both osteoclast and macrophage deficiencies, but only in those tissues which could be reached by CSF-1 from the circulation. Despite severe quantitative macrophage deficiencies, the op/op mice demonstrate normal in vivo phagocytosis and immune functions suggesting that CSF-1 dependent macrophages do not contribute significantly to those processes in vivo. On the other hand, the op/op mice demonstrate severe secondary deficiencies of TNF-alpha, IL-1 alpha, and G-CSF suggesting that major function of CSF-1 dependent macrophages is the release of monokines.
Leukemia 1993 Aug
PMID:In vivo role of macrophage growth factors as delineated using CSF-1 deficient op/op mouse. 836 Dec 13

The relationship between cytokine production patterns and immunophenotype marker profiles was studied in a panel of 18 T cell lines originating from various types of hematological malignancies and from human T cell lymphotropic virus-I (HTLV-I)-transformed cells. The production of 11 different cytokines by both unstimulated and phytohemagglutinin (PHA)-stimulated cells was tested. The production of interleukin-1 alpha (IL-1 alpha), IL-2, IL-3/granulocyte-macrophage colony stimulating factor (GM-CSF), IL-4, IL-5, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta and interferon-gamma (IFN-gamma) by some of the cell lines was detected, and no cell line produced IL-1 beta or IFN-alpha. All 4 cell lines producing IL-1 alpha also produced other inflammatory cytokines, namely, IL-6, TNF-alpha and TNF-beta, but they did not produce IL-2. The IL-1 alpha-producing cell lines had the phenotype of mature, activated T cells, regardless of leukemia or transformant origin (TdT-, CD4+, CD8-, IL-2R+, HLA-DR+) and all were HTLV-1+. However, the production of other cytokines followed a random distribution, and no relationship emerged between cytokine production patterns and alpha/beta or gamma/delta type of T cell receptor (TcR) expression, immunophenotypic marker profiles, or the clinical origin of the cells. These results thus show that human leukemia and HTLV-I-transformed T cell lines can produce a large number of biologically active cytokines and that, except for the association of inflammatory cytokine production with mature activated cells, random patterns of cytokine production reflect the individuality of leukemia cell lines.
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PMID:Multiple and heterogeneous patterns of cytokine production in 18 leukemia and in vitro transformed mature T cell lines reflect the individuality of human leukemias. 849 92

Leukaemia inhibitory factor (LIF) is a secretory glycoprotein produced by tumour, mesenchymal and haemopoietic cells. LIF has been found to have pleiotropic actions that include the capacity to regulate cell differentiation, promote acute-phase protein synthesis and stimulate calcium release in bone explants. In view of its similarity to other cytokines that affect cartilage metabolism, the effects of LIF on proteoglycan resorption were examined in pig cartilage explants. Endotoxin-free recombinant mouse LIF was found to produce a dose-dependent increase in sulphated glycosaminoglycan (S-GAG) release (ED50 = 123 U/ml, approx. 25-50 pM). Statistically significant stimulation was observed with doses of 100 U/ml or greater. When pig cartilage was stimulated with maximum concentrations of LIF and either interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha), in each case a significantly greater release of S-GAGs was observed than with the respective cytokines alone (P < 0.05). Comparison of the areas under the curves showed that the action of LIF was additive, and not synergistic with other catabolic cytokines. Dose-response studies showed that transforming growth factor beta (TGF beta) produced a partial inhibition of LIF-stimulated release of S-GAGs (ED50 = 4.5 U/ml). Statistically significant inhibition was observed with doses of 2 U/ml or greater. These results showed that LIF stimulated proteoglycan resorption in vitro and that this effect was modulated by other cytokines. Whether LIF contributes to the progressive destruction of cartilage in septic or chronic inflammatory arthritis remains to be determined.
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PMID:Leukaemia inhibitory factor stimulates proteoglycan resorption in porcine articular cartilage. 851 24

Polypeptide 48 is a 48,000 MW protein, originally isolated from conditioned media of some human leukaemic cell lines, that induces differentiation and cytolytic activity in HL-60 promyelocytic leukaemia cells and activates human peripheral blood monocytes to secrete interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha). In the present study we examined the effects of p48 on the accumulation of a series of monokine transcripts, including TNF-alpha, IL-1 alpha, IL-1 beta and IL-6, in human peripheral blood monocytes and the myeloid/monocyte cell lines HL-60 and U937. Using reverse transcriptase polymerase chain reaction (RT-PCR) and Northern blot analysis, p48 was found to induce accumulation of TNF-alpha, IL-1 alpha and IL-1 beta mRNA in peripheral blood monocytes, HL-60 and U937 cells. IL-6 mRNA was found to be increased in p48-stimulated peripheral blood monocytes but not HL-60 or U937. Thus, the secretion of IL-1 and TNF-alpha by p48-stimulated monocytic cells was associated with up-regulation of cytokine mRNA, suggesting that p48 leads to increased transcription or mRNA stability in these cells. As U937 and HL-60 are likely to represent premonocyte stages of haemopoietic differentiation, it is possible that the effect of p48 on IL-6 mRNA, in contrast to its effect on TNF and IL-1, requires cells to be at a later differentiation step.
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PMID:Up-regulation of cytokine mRNA in human monocytes and myeloid cell lines by the differentiation/activation factor p48. 855 86

Using a modification of the autologous mixed lymphocyte/tumour cell culture (MLTC), it is demonstrated here that lymphocytes from chronic-phase myelogenous leukaemia (CML) patients (n = 58), but not from their HLA-identical siblings, proliferated upon coculture with autologous tumour cells. However, in most cases, the level of proliferation measured was low (stimulation index < 3, n = 37). This was most likely related to the amount of interleukin-10 (IL-10) released into the culture medium by the CML cells, because addition of neutralizing anti_IL-10 serum to MLTC markedly enhanced proliferative responses. In addition, supplementation of media with IL-1 alpha further enhanced proliferative responses and a combination of anti-IL-10 serum and IL-1 alpha was more effective than either agent alone. Only HLA-DR-matched CML cells, but not HLA-DR-mismatched CML cells or matched or mismatched PBMC restimulated proliferation of IL-2-dependent T cell lines derived from MTLC supplemented with IL-1 alpha and anti-IL-10 serum. The responding cells under these conditions were predominantly CD4+ and secreted IL-2, and interferon gamma; some secreted IL-4, but none secreted IL-10. These data therefore suggest the existence of an HLA-DR-restricted DTH/Th1-type of tumour-specific immunity in CML patients, which may be down-regulated in vitro by excessive secretion of IL-10 together with depressed secretion of IL-1.
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PMID:Cellular immune responses to autologous chronic myelogenous leukaemia cells in vitro. 864 Aug 48

Leukaemia inhibitory factor (LIF) is a pleotropic cytokine, regulating differentiation, cell growth, cachexia and inflammation. Using the reverse transcription-polymerase chain reaction (RT-PCR) we found that, in culture, normal human keratinocytes (KC) expressed mRNA transcripts for both LIF and the LIF receptor. In the conditioned medium (CM), constitutive LIF protein production was barely detectable but stimulation of KC with 10 ng/ml of either interleukin (IL)-1 alpha, or IL-8, for 24 h, resulted in small but significant increases (P < 0.05) in LIF protein, as measured by enzyme-linked immunosorbent assay. After culture in media containing 1.5 mmol/l calcium, a time-dependent increase in LIF mRNA was seen up to 72 h (an 8.5-fold increase), over levels in cells cultured in 0.05 mmol/l calcium. A large increase in LIF protein in the CM (from 1.15 +/- 0.15 pg/ml to 178.7 +/- 75.7 pg/ml) was seen 72 h after a switch to media containing 1.5 mmol/l calcium (P = 0.05). Twenty-four hours after stimulation of human KC in culture with 10 ng/ml recombinant LIF, a twofold increase in both IL-1 alpha and IL-8 protein in the CM (P < 0.05) was observed. In normal human scalp and foreskin, the epidermis was shown to contain LIF protein by immunostaining. LIF staining was found throughout the epidermis, and in the cells of the outer layer of the root sheath. Thus, KC synthesize LIF in vitro and in vivo.
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PMID:Leukaemia inhibitory factor is expressed by normal human keratinocytes in vitro and in vivo. 873 19

Implantation biology is now at a stage where experimental science will be very productive in answering basic questions about the ability of an embryo to implant. The advancement of our knowledge of cytokines and growth factors has been critically important in fuelling the recent new understanding of embryo implantation. Specifically, our increased knowledge of the interleukin (IL)-1 system, as well as leukaemia-inhibiting factor (LIF), epidermal growth factor and colony-stimulating factor-1, and the availability of recombinant protein, specific antibodies and knockout mice, have led to a more detailed outline of implantation events. LIF and IL-1 are the two systems where recent advances have suggested their importance in implantation events. Recently, LIF has been shown in mice to be an endometrial requirement for implantation and embryo development. Although LIF is a pleiotropic molecule, with many interactions in multiple body tissues, in the uterus, concentrations are elevated on day 4 of pregnancy. Experiments with knockout mice have shown the requirement for endometrial LIF for successful implantation. The IL-1 system, consisting of two agonists (IL-1 alpha and IL-1 beta), two receptors (IL-1R types I and II) and the homologous IL-1 receptor antagonist (ra), has also been studied. Knowledge that the embryo secretes IL-1 suggested the interaction between embryonic IL-1 and endometrial receptor, which has been shown to occur. IL-1R type I is plentiful on endometrial epithelial cells and appears to interact with embryonically secreted IL-1 beta to favour implantation. Such implantation events in vivo in mice are blocked by the introduction of large quantities of IL-1ra, consistent with the hypothesis that appropriate interactions between agonist and receptor at the level of the endometrial surface are a requisite for successful implantation. As more specific information on each cytokine or growth factor system comes to light, more complete information on the multiple molecular steps of implantation will become apparent. However, it is clear that no single cytokine or growth factor will be able to explain the complicated events of embryo implantation. Such an important necessary phenomenon has multiple redundancies. The interactions between cytokines and growth factors are becoming increasingly apparent and will need more experimental evidence before a full understanding of implantation is available.
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PMID:Role of embryonic factors in human implantation. 874 98

Blast cells derived from patients with acute myelogenous leukemia (AML) were cultured in the presence of interleukin-13 (IL-13). IL-13 did not cause statistically significant alterations of AML blast proliferation when cells were cultured in medium alone or together with IL-4, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. In contrast, IL-13 inhibited constitutive AML blast secretion of IL-1 alpha, IL-1 beta, IL-6, tumor necrosis factor alpha, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. IL-4 caused a similar inhibition of constitutive cytokine secretion as IL-13, but IL-13 caused no additive inhibition in the presence of IL-4. In contrast to IL-4 which increased AML blast release of IL-1 receptor antagonist, IL-13 caused no significant alteration of blast release of the receptor antagonist. IL-13 inhibited cytokine secretion also in the presence of neutralizing IL-4 and IL-10 antibodies and when AML blasts were cultures in serum-free conditions. We conclude that IL-13 has a direct and nontoxic inhibitory effect on constitutive AML blast cytokine secretion.
Leukemia 1996 Sep
PMID:Effects of interleukin-13 on cytokine secretion by human acute myelogenous leukemia blasts. 875 69

Serum levels of cytokines and in vitro cytokine production by lymph node mononuclear cells (LNMC) were studied in four patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD) or AILD-type T cell lymphoma. An increased level of serum interleukin-6 (IL-6) was detected on initial diagnosis in both of two patients examined. Spontaneous production of IL-6 by LNMC was detected in all four patients studied. Immunosuppressive therapy with cyclosporin A (CsA) was attempted in a 68-year-old man, who was refractory to intensive combination chemotherapy. The increased level of IL-6 in this patient decreased to normal within 3 weeks of CsA administration and the patient became symptom-free. One and a half months later, the IL-6 level gradually increased along with clinical exacerbation. We also measured serum levels of IL-1 alpha, IL-2, IL-4, IFN-alpha, gamma and TNF-alpha in parallel with IL-6, but these factors were only sporadically detected. IL-6 production by LNMC was stimulated by IL-2 but inhibited by CsA. These observations suggest that IL-6 is one of the important cytokines to be involved in the pathophysiology of AILD and CsA is a useful reagent for relieving symptoms.
Leukemia 1996 Sep
PMID:Increased levels of interleukin-6 (IL-6) in serum and spontaneous in vitro production of IL-6 by lymph node mononuclear cells of patients with angio-immunoblastic lymphadenopathy with dysproteinemia (AILD), and clinical effectiveness of cyclosporin A. 875 70

Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all-trans retinoic acid (ATRA) on the in vitro autocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1 alpha, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-alpha were tested with and without ATRA addition. After 5 d exposure to ATRA 10(-6) M APL-treated samples showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a significant increase of IL-1 alpha (p = 0.01) production, if compared to untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4 productions; G-CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G-CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF-alpha was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL-6 was more than twice as high in ANLL non-APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the exhaustion of the leukemic clone upon treatment with ATRA.
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PMID:All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells. 898 93


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