Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00035 (CSF)
 30,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the in vivo effects of recombinant human interleukin-6 (rhIL-6) on hematopoiesis in eight healthy and nine irradiated cynomolgus monkeys. Of the healthy animals, three received rhIL-6 alone (10 micrograms/kg/d, subcutaneously [SC]), one received rhIL-6 in combination with rhIL-3 (10 micrograms/kg/d, SC), one received rhIL-6 in combination with recombinant cynomolgus granulocyte-macrophage colony-stimulating factor (rcGM-CSF; 10 micrograms/kg/d, SC), two received rhIL-6 in combination with recombinant human granulocyte-CSF (rhG-CSF; 10 micrograms/kg/d, SC), and one received rhIL-6 in combination with recombinant human leukemia inhibitory factor (rhLIF; 10 micrograms/kg/d, SC). All animals were treated for at least 2 weeks with rhIL-6 or the above mentioned combinations. rhIL-6 alone significantly increased the peripheral blood platelet counts (2- to 3.5-fold). The platelets reached a plateau between days 10 and 15 of treatment. No synergistic effects on platelet numbers were observed when rhIL-6 was combined with rhIL-3, rcGM-CSF, rhG-CSF, or rhLIF. In addition to rhIL-6, only rhLIF increased the platelet numbers when administered alone. To test whether rhIL-6 might also protect the animal from thrombocytopenia or shorten the time of thrombocytopenia after irradiation, we treated nine animals with total body irradiation (3.8 Gy). Six of the animals were additional treated with rhIL-6 (4 with 10 micrograms/kg/d; and 2 with 100 micrograms/kg/d) from day -1 or +1 to day 28 post irradiation. In these animals, rhIL-6 at the same dose effective in healthy animals (10 micrograms/kg/d) was not capable of protecting the animals from platelet nadir. However, when pegylated rhIL-6 was used at a dosage of 100 micrograms/kg/d post irradiation, the mean of the nadirs was 71,000/microL as compared with 39,000/microL in control animals and the time of thrombocytopenia was shorter (3 v 5 days). In all animals (healthy and irradiated), rhIL-6 did not increase the number of bone marrow megakaryocytes but induced a right shift of DNA ploidy in megakaryocytes. These data suggest that IL-6 acts as "thrombopoietin"-like activity, but not as "megakaryocyte-CSF"-like activity.
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PMID:In vivo effects of interleukin-6 on thrombopoiesis in healthy and irradiated primates. 768 32

To investigate the role of peritoneal mesothelial cells in regulating hematopoiesis, as well as inflammation, healing, and tissue regeneration processes, long-term cultures of peritoneal mesothelial cells from human endocavitarian fluids were established. The purity of the cell population was assessed by morphologic and immunocytochemical criteria. Five peritoneal mesothelial cell cultures were analyzed for cytokine expression. Macrophage colony-stimulating factor (M-CSF), granulocyte-CSF (G-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-6 transcripts were constantly but variably detected throughout the culture period, while granulocyte-monocyte-CSF (GM-CSF) expression started as the cell culture aged. No IL-2, IL-3, IL-4, IL-5, or IL-7 transcripts were detected in the same samples. Corresponding cytokine activities were detected in the supernatants of the cultures. Peritoneal mesothelial cells proliferated after the addition of exogenous IL-1 beta or IL-1 alpha, whereas the addition of recombinant GM-CSF, G-CSF, M-CSF, or IL-6 failed to trigger proliferation. IL-1 receptor type I transcripts were detected in peritoneal mesothelial cells. Moreover, IL-1 was able to upregulate the expression of the genes that code for G-CSF, GM-CSF, IL-1 alpha, and IL-1 beta in these cells. These data indicate that peritoneal mesothelial cells produce many cytokines and suggest that IL-1 is a regulatory molecule for peritoneal mesothelial cells.
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PMID:Human peritoneal mesothelial cells produce many cytokines (granulocyte colony-stimulating factor [CSF], granulocyte-monocyte-CSF, macrophage-CSF, interleukin-1 [IL-1], and IL-6) and are activated and stimulated to grow by IL-1. 128 Apr 80

Sera of 25 healthy controls and 75 patients suffering from myelodysplastic syndromes (MDS) were investigated for serum concentration of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), erythropoietin (Epo), and tumor necrosis factor-alpha (TNF-alpha). According to French-American-British (FAB) classification, 21 refractory anemia (RA), seven refractory anemia with ring sideroblasts (RARS), 15 chronic myelomonocytic leukemia (CMML), 12 refractory anemia with excess of blasts (RAEB), and 20 RAEB in transformation (RAEBt) were examined. TNF-alpha levels were inversely correlated with lower levels of hemoglobin concentration (r = -0.31, p = 0.005), irrespective of the requirements for transfusion in anemic MDS patients. Significant differences in TNF-alpha levels between CMML (26.2 +/- 5.9 pg/ml) and the FAB subgroups (16.1 +/- 1.6 pg/ml) were detected. There was an overall inverse relationship between the level of erythropoietin and the degree of anemia, but a wide range of Epo response between patients with similar hemoglobin concentrations. Serum levels of IL-1 alpha and GM-CSF were undetected in most of the patients. In 57% of the samples there were detectable levels of G-CSF, without a correlation of the serum levels with blood cell counts, nor with any of the FAB subcategories. Overall, 29% and 25% of the patient sera exhibited elevated IL-3 and IL-6 levels, respectively. There was no correlation of the serum levels with any of the blood counts, other cytokines, nor FAB subcategories. In conclusion, simple negative feedback mechanism between a specific cytokine and the production of blood cells seems not to be the case in MDS, except for red cell production and erythropoietin concentration. Our data may suggest the involvement of TNF-alpha in the pathogenesis of anemia in MDS.
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PMID:Measurement of serum cytokine levels in patients with myelodysplastic syndromes. 128 Jul 51

In a search for specific serum markers with prognostic impact in Hodgkin's Disease (HD), we evaluated the clinical significance of several cytokines (IL-1 beta, IL-2, IL-3, IL-6, G-CSF, GM-CSF, TNF-alpha) and soluble forms of membrane-derived antigens (sCD4, sCD8, sCD23, sCD25, sCD30) in the serum of patients with untreated HD. Elevations of three groups of serum factors were observed: Firstly, elevations of the hematopoietic cytokines GM-CSF (detected in 39%), IL-6 (57%) and IL-3 (13%), which occurred simultaneously in the majority of the cases; secondly, simultaneous elevations of the inflammatory cytokines TNF-alpha and IL-1 beta (detected in 7%); and finally, elevations of membrane-derived activation antigens sCD8, sCD25, and sCD30. While the cytokine levels did not correlate with other obvious parameters, the membrane-derived activation antigens sCD8, sCD25 and sCD30 were associated with a poor prognosis. Only sCD30 correlated with disease activity and holds promise for the follow-up of patients in remission. Further investigations of these parameters at the cellular level might help to elucidate the enigmatic biology of HD.
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PMID:The clinical significance of cytokines and soluble forms of membrane-derived activation antigens in the serum of patients with Hodgkin's disease. 128 46

Our present study was designed to clarify the mechanism by which the same megakaryocyte progenitor cells respond to various cytokines at different stages of megakaryocyte development. We examined the changes in mRNA expression of granulocyte macrophage colony-stimulating factor receptor beta-subunit (GM-CSFR beta-subunit), which was a common subunit of a high-affinity interleukin-3 receptor (IL-3R) and a high-affinity GM-CSFR, and interleukin-6 receptor (IL-6R) during megakaryocyte development in a human megakaryocytic leukemia cell line (CMK) which could proliferate and/or differentiate in the presence of 12-O-tetradecanoylphorbol 13-acetate (TPA), IL-3, GM-CSF, and IL-6. We found that GM-CSFR beta-subunit mRNA was expressed constitutively in CMK cells and was transiently down-regulated by TPA and IL-6, while the expression of IL-6R mRNA was increased by TPA in association with the differentiation of megakaryocytes. Furthermore, the TPA-induced down-regulation of GM-CSFR beta-subunit mRNA expression and its recovery were blocked by cycloheximide (CHX), a protein synthesis inhibitor, suggesting that these modulations required de novo protein synthesis. These findings imply that multi-lineage cytokines such as GM-CSF and IL-3 may contribute preferentially to the regulation of the earlier development of megakaryocyte progenitor cells with high densities of multi-lineage cytokine receptors, while IL-6 may be limited in its action to supporting the maturation of more differentiated megakaryocyte progenitor cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of GM-CSF receptor beta-subunit and interleukin-6 receptor mRNA expression in a human megakaryocytic leukemia cell line. 129 Sep 64

Cytokines (IL-1, sIL-2R, IL-3, IL-6, TNF-alpha, IFN-gamma, GM-CSF and neopterin) were measured in sera of 37 patients with hypertensive disorders of pregnancy, 10 healthy pregnant and 10 healthy non-pregnant controls. With the exception of neopterin (p = 0.004) there were no statistically significant differences in cytokine concentrations between healthy pregnant and non-pregnant controls. No statistically relevant differences between healthy pregnant women and hypertensive patients could be found in cytokines of T-lymphocytic origin except GM-CSF in patients with HELLP syndrome (p = 0.02). Elevated levels of IL-6, TNF-alpha and neopterin were observed in hypertensive women. Differences to healthy pregnant controls were statistically significant for IL-6 (p = 0.008), TNF-alpha (p = 0.009) and neopterin (p = 0.04) and were more pronounced in severe forms of the disease. These 3 parameters of monocytic origin showed significant positive correlations amongst each other. A participation of cell-mediated immunity (especially monocytes/macrophages) in the pathomechanism of hypertensive disorders of pregnancy can thus be assumed.
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PMID:[Cellular immunity in pregnancy-induced hypertensive diseases]. 129 33

The measurement of cytokine mRNA levels is of fundamental importance in the understanding of diverse pathological states. We present a simplification of a polymerase chain reaction-based technique which permits the simultaneous measurement of up to 20 cytokine mRNAs, together with those of several other cellular products, including beta 2-microglobulin and beta-actin. The technique makes use of internal standards bearing multiple PCR primer sites which are identical to those on the mRNAs to be assayed. Known quantities of the standards are added to the cellular RNA and the mixture is co-reverse transcribed and co-amplified. The simplifications described here are based on the fact that each pair of amplicons accumulates in a constant ratio even in the plateau phase of amplification. As a result, no preliminary experiments to determine the limits of the exponential phase of amplification are necessary; the same number of cycles may be chosen for all the mRNAs to be measured, whatever their level in the mixture might be; pipetting errors are avoided since all calculations are based upon the relative quantities of co-amplified material. Here we illustrate the method through a quantitative study of the expression of cytokine mRNAs in U373 human astrocytoma cells before and after stimulation with IL-1 beta. Quantitation was carried out either by incorporating radioactivity in the amplicons or by fluorescence measurements after propidium iodide staining. Only very low numbers of transcripts for IL-6, IL-8, CSF-1, MCP-1 and either Gro alpha or Gro beta were detectable in unstimulated cells. The levels of these cytokine mRNAs increased dramatically following IL-1 beta stimulation and, in addition, transcription of IL-1 beta, TNF alpha, GM-CSF, G-CSF, Gro gamma and MCP-1, some of which have not previously been detected in U373, was initiated in the stimulated cells. At the same time we found that transcripts for IL-2, IL-3, IL-4, IL-5, IFN gamma, huMlP1 alpha and huMlP1 beta were totally absent in this cell line. These results suggest a potentially important role for astrocytes in the local amplification of inflammatory responses in the brain.
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PMID:Simultaneous quantitation of cytokine mRNAs in interleukin-1 beta stimulated U373 human astrocytoma cells by a polymerisation chain reaction method involving co-amplification with an internal multi-specific control. 129 3

Fu-Ling, the sclederma of Poria cocos (Schw.) Wolf, has long been used as a sedative and diuretic. However, data in this report suggest that Fu-Ling is a potential suppressor of cytokine secretion from human peripheral blood monocytes under in vitro condition. Monocyte culture medium containing 10% of Fu-Ling extract significantly inhibited secretion of TNF-alpha, IL-beta, IL-6 and GM-CSF from the monocyte monolayer. However, as Fu-Ling extract content was gradually reduced, cytokine secretion was augmented in comparison with the cytokine secretion in drug-free controls. This augmentative effect resulted from the trace amount (1.24 ng/ml in 0.62% of Fu-Ling extract) of lipopolysaccharide (LPS) which contaminated the Fu-Ling extract during the preparation process, since TNF-alpha, IL-1 beta and IL-6 secretion induced by 0.62% Fu-Ling extract could be significantly inhibited by polymyxin B, an LPS inhibitor. Furthermore, the amounts of TNF-alpha IL-1 beta and IL-6 induced by 1 ng/ml of LPS without the presence of drug were more than that induced by 0.62% of Fu-Ling extract. Thus, cytokine secretion induced by LPS contamination (1.24 ng/ml) in the Fu-Ling extract was partially suppressed by 0.62% of the Fu-Ling extract itself. GM-CSF secretion in the medium containing 0.62% of Fu-Ling extract was not induced by LPS since: a) GM-CSF induced by 0.62% Fu-Ling extract could not be inhibited by polymyxin B; b) LPS at 1 ng/ml showed no activity indicating induction of GM-CSF secretion.
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PMID:Suppression of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and granulocyte-monocyte colony stimulating factor secretion from human monocytes by an extract of Poria cocos. 130 45

The effects of different recombinant human cytokines and cytokine inhibitors were compared in a culture system in which cell contact with mutant EL-4 thymoma cells of murine origin efficiently stimulates human B cell proliferation and Ig secretion in conjunction with human T cell supernatant. IL-1 alpha, IL-1 beta, TNF-alpha, and IL-2 co-stimulated B cell proliferation and IgM, IgG, and IgA secretion, whereas IL-3, IL-4, IL-5, IL-6, IFN-gamma, or GM-CSF had weak or no activity in this regard. In contrast, TGF-beta 1 was strongly inhibitory. A very strict hierarchy of cytokine interactions was found in that IL-1 was necessary to induce TNF-alpha responsiveness, and TNF-alpha the IL-2 responsiveness, of the B cells. Most likely the small number of starting B cells in the present assay (300 FACS-separated B cells/200 microliters) minimized the effects of autocrine B cell factors. IL-4 together with IL-1 induced IgE secretion, and the IgE secretion was further increased by TNF-alpha. IFN-gamma had no modulatory effect on the IL-4 dependent IgE response in this system. Pretreatment of B cells with IL-1R antagonist (IL-1ra, which binds to IL-1R) or addition of soluble TNF receptor type 1 (sTNF-R55, which binds to TNF) completely inhibited the IL-1 or TNF-alpha effects, respectively. This occurred in a specific manner; the inhibition was reversed by a large excess of cytokine. IL-1ra also inhibited a B cell response induced by PMA-preactivated EL-4 cells alone. Because B cells responding to such preactivated EL-4 cells did not acquire TNF-alpha responsiveness, no IL-1 was apparently involved under this assay condition. It appears, therefore, 1) that IL-1ra can act on B cells and 2) that this antagonist may not only block IL-1R, but may provide a direct or indirect inhibitory signal interfering even with IL-1-independent B cell activation.
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PMID:Effects of eleven cytokines and of IL-1 and tumor necrosis factor inhibitors in a human B cell assay. 131 59

One of the morphologic hallmarks of human gliomas are inflammatory infiltrates with accumulation of macrophages in the tumor site. The signals leading to the macrophage response are only at the beginning of being understood. Novel chemotactic factors that have recently been characterized as secretory products of glioblastoma cells may attract mononuclear cells from the blood. Within the tumor tissue blood-derived monocytes and macrophages of the brain tissue, the microglial cells, may increase in cell numbers due to tumor-derived growth factors. Both astrocytoma cell lines and cultured astrocytes have been shown recently to produce granulocyte-macrophage (GM)-CSF. We show that in vitro not only astrocytoma but also glioblastoma cell lines secrete GM-CSF when stimulated with TNF-alpha or IL-1. However, there is no evidence for GM-CSF production by glioblastoma cells in vivo: fresh tumor samples lack the mRNA for GM-CSF and the protein is not detectable in the tumor cyst fluids or the cerebrospinal fluids of glioblastoma patients. This contrasts IL-1 and IL-6 that are detectable in the tumor cyst fluids and IL-6 also in the cerebrospinal fluids of the patients. Unlike GM-CSF, transforming growth factor-beta 2 mRNA is expressed in ex vivo tested glioblastoma tissues. Absence of GM-CSF in vivo may be explained by the presence of tumor-derived inhibitory factors, such as transforming growth factor-beta 2 and PGE which suppress GM-CSF production by glioblastoma cells in vitro. The accumulation of macrophages at the tumor site may be due to local elaboration of chemoattractants and/or not yet defined growth factors rather than due to GM-CSF production.
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PMID:Granulocyte-macrophage colony-stimulating factor (GM-CSF) production by glioblastoma cells. Despite the presence of inducing signals GM-CSF is not expressed in vivo. 131 29


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