Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Commercially produced biological medicines may contain cytokines secreted by mammalian cell lines. Several such cell lines were found to produce interleukin 6 and, after stimulation, to secrete interleukin 1, tumour necrosis factor, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. High levels of interleukin 6 were detected in several vaccines and rDNA-derived proteins, and certain vaccines contained interleukin 1, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor. Some preparations of human monoclonal antibodies were also found to contain interleukin 1 and tumour necrosis factor. Cytokines may contribute to certain types of adverse reactions to these products.
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PMID:Demonstration of cytokines in biological medicines produced in mammalian cell lines. 247 47

Peritoneal macrophages elicited by Lactobacillus casei YIT9018 (LCEPM) were incubated in culture for 18 h with L. casei; the culture supernatant (LCM) was then harvested and tested for its ability to increase the cytostatic activity of resident peritoneal macrophages (RPM) and LCEPM. Treatment of RPM with LCM induced activation of macrophages to a cytostatic state against L929, Colon 26, P815, P388D1 and L1210 cells. A combination of recombinant human tumor necrosis factor (rhTNF), recombinant mouse TNF (rmTNF), recombinant human interleukin-1 (rhIL-1) or bacterial lipopolysaccharide with recombinant mouse interferon gamma (rmIFN-gamma) resulted in the synergistic induction of cytostatic activity in RPM. Recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) plus rhTNF increased the cytostatic activity of RPM a little but rmGM-CSF or rhTNF combined with rhIL-1 or alone had no effect. The effect of LCM on RPM was not inhibited by polymyxin B, anti-mTNF antiserum or below 20 U/ml monoclonal anti-rmIFN-gamma antibody (anti-rmIFN-gamma) but was inhibited by more than 40 U/ml anti-rmIFN-gamma, and LCM did not have any interferon antiviral activity. These results suggest that the cytostatic activity of RPM was augmented by the LCM, and that the effect of the LCM may be not due to IFN-gamma, TNF, GM-CSF, IL-1 or a small amount of contaminating lipopolysaccharide.
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PMID:Role of culture supernatant of cytotoxic/cytostatic macrophages in activation of murine resident peritoneal macrophages. 249 78

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a well-characterized hematopoietic growth factor. Recently, using purified recombinant-derived material, we have found that GM-CSF is also a potent activator of mature functional macrophages. Thus, we have found that exogenous GM-CSF augments the primary plaque-forming response to sheep red blood cells and that this effect is due to upregulation of Ia antigen expression and interleukin 1 production by the macrophages. We also show that GM-CSF inhibits the replication of Trypanosoma cruzi in cultured peritoneal macrophages and causes an accelerated clearance of Salmonella typhimurium from the peritoneal cavity of mice. These data indicate that GM-CSF is a multifunctional molecule stimulating both hematopoiesis and mature macrophage function.
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PMID:Granulocyte/macrophage colony stimulating factor. A potent activation signal for mature macrophages and monocytes. 249 41

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and HTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-1 alpha, IL-1 beta and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.
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PMID:Expression of cytokine mRNA in leukemic cells from adult T cell leukemia patients. 250 74

Following exposure of cultured human synovial cells to human recombinant interleukin 1 alpha (IL-1 alpha), we demonstrate the appearance of factors in the supernatant which stimulate human polymorphonuclear leukocyte (PMN) locomotion and elevate intracellular free calcium ([Ca++]i). The production of these factors can be abolished by actinomycin D or dexamethasone but not by cyclo-oxygenase or lipoxygenase inhibitors. In vivo, the supernatant induces a rapid accumulation of PMNs in rabbit skin following intradermal injection. These activities were not due to IL-1 itself, tumour necrosis factor (TNF alpha) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Such factors may play an important role in inflammatory responses involving IL-1.
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PMID:PMN stimulation by factors from IL-1-treated human synovial cell cultures. 250 46

The purpose of this study was to examine the effect of lithium chloride (LiCl) on human monocytes. Patients undergoing lithium therapy have elevated white blood cell counts. Since both tumor necrosis factor alpha (TNF alpha) and interleukin 1 (IL-1), which are secreted by monocytes, can stimulate endothelial cells to produce granulocyte-macrophage colony-stimulating factor (GM-CSF), we determined whether lithium-stimulated monocytes produced TNF alpha and/or IL-1. Normal human monocytes were incubated for 24 h with medium (negative control), lipopolysaccharide (positive control), or LiCl (0.05-50 mM). The supernatants were removed and assayed for IL-1 and TNF alpha secretion using the D10.G4.01 and L929 assays, respectively. Lithium did not stimulate IL-1 secretion but did stimulate TNF alpha secretion (5-10 U/ml of TNF alpha per 2 x 10(5) monocytes). The increased secretion of TNF alpha was associated with a fourfold increase in TNF alpha mRNA. TNF alpha activity in the supernatants was neutralized by a monoclonal antibody against human TNF alpha but not by antibody against human albumin. Other alkali metals such as rubidium and cesium did not stimulate monocytes to secrete TNF alpha. These data indicate that one mechanism by which Li may cause granulocytosis is through a transcriptional enhancement of TNF production and subsequent secretion by monocytes.
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PMID:Lithium chloride stimulates human monocytes to secrete tumor necrosis factor/cachectin. 255 37

The effects of hematopoietic growth factors on in vitro human megakaryocytopoiesis were studied using a serum-depleted culture system. Both recombinant interleukin-3 (r-IL-3) and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) increased megakaryocyte (MK) colony formation (P less than .01) above that observed in baseline cultures. Recombinant interleukin-4 (rIL-4) and interleukin 1 alpha (rIL-1 alpha) failed either to promote MK colony formation alone or to increase rIL-3 or rGM-CSF promoted colony formation. Recombinant erythropoietin (rEpo) and purified thrombocytopoiesis-stimulating factor (TSF) did not increase (P greater than .05) MK colony formation when added alone but synergized with rIL-1 alpha, leading to a twofold increase in MK colony formation. Such a synergistic relationship was not observed between rIL-4 and rEpo. In addition, TSF enhanced the ability of rIL-3 but not rGM-CSF to promote MK colony formation. Addition of rEpo to optimal or suboptimal concentrations of rGM-CSF or suboptimal concentrations of rIL-3 resulted in a significant increase (P less than .05) in the total number of MK-containing colonies, due to the appearance of multilineage colonies containing MKs. The addition of rEpo to optimal concentrations of rIL-3 resulted in increased numbers of multilineage colonies containing MKs; however, the number of total MK-containing colonies was not significantly increased when compared to assays containing rIL-3 alone. By contrast, transforming growth factor-beta (TGF-beta) inhibited both rIL-3, and rGM-CSF promoted MK colony formation, with optimal inhibition resulting in a 35%-45% reduction of MK colony formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interacting cytokines regulate in vitro human megakaryocytopoiesis. 264 84

The inflammatory effects of intradermal injections of the human recombinant cytokines interleukin 1 (IL-1), granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF alpha) have been assessed in rabbit skin, and compared with the effects of a novel polymorphonuclear leucocyte (PMN)-stimulating activity (PSA) produced by IL-1-treated human synovial cell cultures. IL-1 (84 fmol) and GM-CSF (10 pmol) caused increases in vascular permeability with a delayed onset, as assessed by the dermal accumulation of intravenously-administered 125I-human serum albumin. These cytokines also stimulated extravascular accumulation of PMNs. In contrast, PSA-containing supernatant caused a more rapid and prolonged increase in vascular permeability and PMN accumulation. TNF alpha (84 fmol) was unable to stimulate either of these responses. The increases in vascular permeability and PMN accumulation following IL-1 administration in vivo may be a consequence of the local generation of PMN-stimulating activity by connective tissue cells, such as the activity produced by IL-1-treated synovial cell cultures that we have described.
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PMID:Increased vascular permeability and polymorphonuclear leucocyte accumulation in vivo in response to recombinant cytokines and supernatant from cultures of human synovial cells treated with interleukin 1. 264 20

Levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the peritoneal and pleural cavity fluid of two lines of GM-CSF transgenic mice were abnormally high (up to 120,000 U/ml), often exceeded the elevated serum GM-CSF levels in these mice and correlated with the increased number of macrophages present. In the peritoneal fluid, the only significant elevations of IL-1 levels were seen in moribund male-line transgenic mice. In contrast, IL-1 levels in pleural cavity fluid of male-line transgenic mice were clearly higher than those in littermate control mice or female-line transgenic mice. In male-line transgenic mice, IL-1 levels in both peritoneal and pleural cavities correlated with local macrophage numbers. Endotoxin was detectable in the peritoneal cavity fluid from some mice of all types but did not correlate with elevated IL-1 levels. No correlation was observed between levels of GM-CSF or IL-1 in the peritoneal cavity and the development of fibrotic nodules in the peritoneal cavity or gut congestion, two lesions common in male-line GM-CSF transgenic mice. The data suggest that the elevated levels of IL-1 in GM-CSF transgenic mice may be the consequence of stimulation by GM-CSF of IL-1 production by the elevated numbers of macrophages in these mice.
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PMID:Elevated levels of GM-CSF and IL-1 in the serum, peritoneal and pleural cavities of GM-CSF transgenic mice. 266 8

A plastic-adherent mononuclear cell population in human bone marrow produces non-plastic-adherent nucleated cells in liquid cultures. These cells can be harvested from the culture medium and a proportion of them can be identified as granulocyte-macrophage colony-forming cells (GM-CFC) by plating them in semi-solid cultures with granulocyte-macrophage colony-stimulating factor (GM-CSF). The generation of GM-CFC from their plastic-adherent precursors can be amplified considerably by adding 5637 conditioned medium (CM) to the liquid phase of the adherent cell cultures. This effect of 5637 CM cannot be reproduced by recombinant (r) GM-CSF or interleukins (ILs) 1, 3 or 6 if they are added singly to the culture medium. In contrast, the combination of GM-CSF + IL-1 equalled or surpassed the activity of 5637 CM. The combinations of rGM-CSF + rIL-3 and rGM-CSF + IL-6 also mimicked the activity of 5637 CM but less effectively than GM-CSF + IL-1.
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PMID:An in vitro model for the production of committed haemopoietic progenitor cells stimulated by exposure to single and combined recombinant growth factors. 267 54


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