Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxin (lipopolysaccharide, LPS) has the property of inducing tolerance to its own biological effects. This phenomenon has been extensively studied in animal models but only few studies exist on the regulation in humans. Here we describe experiments designed to determine the cytokine regulation and cellular changes in humans during induction of LPS tolerance after repeated LPS injections. Intravenous administration of purified LPS Salmonella abortus equi to cancer patients induces high amounts of circulating tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-8 (IL-8), granulocyte colony-stimulating factor (G-CSF), and macrophage colony-stimulating factor (M-CSF). Repeated injections of LPS at daily intervals resulted in a marked downregulation of the cytokine response and in the case of TNF-alpha, IL-8, G-CSF, and M-CSF the cytokine response was reduced to baseline levels. In contrast, significant increases in serum IL-6 were detected up to day 5 of repeated LPS injections. Hematological changes included transient decreases in WBCs affecting granulocytes, monocytes, and lymphocytes, followed by a marked granulocytosis. The drop in WBCs remained unaltered throughout the 5 day course of repeated LPS injections whereas the granulocyte overshoot recovery diminished gradually. When PBMCs of the cancer patients were restimulated ex vivo a marked enhancement of the capacity to produce TNF-alpha, IL-113, and IL-6 occurred, which is in contrast to the decreasing TNF-alpha serum levels obtained in vivo. In parallel, a shift in monocyte subpopulations from CD14+/CD16- to CD14+/CD16+ cells was observed. The data provide evidence that different mechanisms are implicated in the cytokine downregulation following repeated LPS injections to cancer patients. Furthermore, PBMCs from LPS tolerant patients do not demonstrate a reduction in their capacity to produce cytokines.
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PMID:Endotoxin tolerance: regulation of cytokine production and cellular changes in response to endotoxin application in cancer patients. 128 77

In agar culture of post 5-fluorouracil mouse bone marrow cells (FUBM), recombinant rat stem cell factor (rrSCF) synergizes with granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3) or interleukin-6 (IL-6) to stimulate primitive progenitor cells (HPP-CFCs). The addition of recombinant human transforming growth factor beta (rhTGF-beta) to cultures of FUBM containing rrSCF plus rhG-CSF, rrSCF plus recombinant murine (rm)IL-3, or rrSCF plus rhIL-6 resulted in 100% inhibition of colony formation. Highly enriched populations of primitive bone marrow cells were obtained by isolating lineage negative (Lin-), Sca-1-positive (Sca-1+) cells from normal mouse bone marrow. RhTGF-beta inhibited 90% of colony formation stimulated by rrSCF plus rmIL-3 in agar culture of the Sca-1+ cells. RhTGF-beta also inhibited colony formation in agar culture of post FU human bone marrow cells. The synergistic increase in colony formation obtained with recombinant human SCF (rhSCF) plus rhGM-CSF and rhSCF plus rhIL-3 was inhibited by rhTGF-beta (approx. 60% and 87% inhibition, respectively). RhTGF-beta also totally inhibited the erythroid colony formation stimulated by rhSCF plus recombinant human erythropoietin (rhEpo). These data demonstrate that TGF-beta inhibits SCF-stimulated colony formation of mouse and human BM. This inhibition on progenitor cells appears to be a direct action of TGF-beta and is consistent with the target cells of SCF being more primitive progenitors than the CFCs stimulated by the CSFs alone.
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PMID:Transforming growth factor beta inhibits the action of stem cell factor on mouse and human hematopoietic progenitors. 137 30

The biologic effects of endotoxin are attributed to the release of several cytokines, including interleukin-1, interleukin-6, tumor necrosis factor, and the colony-stimulating factors. To investigate the mechanism of endotoxin-induced neutrophilia in dogs, several cell lines known to proliferate selectively in response to recombinant human colony-stimulating factors were examined to determine their responses to recombinant canine granulocyte colony-stimulating factor (rcG-CSF) or recombinant canine granulocyte-macrophage colony-stimulating factor (rcGM-CSF). The murine cell line NFS-60 was found to respond well to rcG-CSF and the human cell line TALL-101 to rcGM-CSF, and these responses were neutralized by antibodies to these recombinant proteins. These bioassays were then used to determine G-CSF and GM-CSF levels in dogs after intravenous endotoxin administration. G-CSF levels increased by 2 h, peaked at 4 h, and had not returned to normal by 24 h after endotoxin. In contrast, GM-CSF was not detectible before or after endotoxin administration.
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PMID:Effect of endotoxin on serum granulocyte and granulocyte-macrophage colony-stimulating factor levels in dogs. 140 42

We studied the production of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-6 (IL-6) by stromal cells from 33 patients with aplastic anemia (AA). Complete, confluent stromal layers were produced by 29 of the 33 samples using the long-term bone marrow culture (LTBMC) system. The concentration of G-CSF, GM-CSF, and IL-6 in culture media with or without interleukin-1 (IL-1) stimulation was determined by an enzyme-linked immunoadsorbent assay (ELISA). The spontaneous production of G-CSF, GM-CSF, and IL-6 did not differ significantly between normal controls and the patients with AA. The ability of stromal cells to release the three hematopoietic growth factors in response to IL-1 was either normal or elevated in all but one patient. We also studied the change in production of G-CSF, GM-CSF, and IL-6 by stromal cells before and after antilymphocyte globulin (ALG) therapy in 16 patients with AA. There was no correlation between the change in production of these cytokines and the response to ALG. In contrast to previous studies that showed a defect in the production of hematopoietic growth factors by stromal cells from patients with AA, the results indicated a normal or elevated production of G-CSF, GM-CSF, and IL-6 by marrow stromal cells in patients with AA.
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PMID:Hematopoietic growth factors released by marrow stromal cells from patients with aplastic anemia. 137 68

The combined effects of five cytokines; recombinant human (rHu) granulocyte colony-stimulating factor (G-CSF), rHu granulocyte-macrophage colony-stimulating factor (GM-CSF), rHu interleukin-1 beta (IL-1 beta), rHu interleukin-3 (IL-3), and rHu interleukin-6 (IL-6) on blast colony formation in methylcellulose by leukemic blast progenitors from 10 patients with acute myeloblastic leukemia (AML) were studied. Combination of G-CSF, GM-CSF, IL-1 beta, and IL-3 stimulated maximum blast colony formation in 9 patients. Further addition of IL-6 reduced the combined effect of the four cytokines on blast colony formation. IL-6 regulates the proliferation of leukemic blast progenitors and may play an important role in the regulation of hematopoiesis.
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PMID:Interleukin-6 reduces the optimal growth in vitro of leukemic blast progenitors from acute myeloblastic leukemia patients. 137 92

Entry into the cell cycle of dormant hematopoietic progenitors appears to be regulated by multiple synergistic factors, including interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), IL-11, and the ligand for c-kit, which is also known as steel factor (SF). We have tested the effects of these and other hematopoietic factors on the proliferation of partially enriched dormant murine progenitors in the presence and absence of serum. In serum-containing cultures, SF and IL-11 interacted to support the formation of multilineage colonies; the level of colony formation was comparable with the colony formation supported by other effective two-factor combinations. In serum-free cultures, colony formation supported by two factors was significantly less than that in serum-containing culture and the most effective two-factor combination in serum-free culture was SF plus IL-3. In serum-free cultures, three-factor combinations consisting of SF, IL-3, and one of IL-6, G-CSF, or IL-11 yielded colony formation that was comparable with that seen in serum-containing cultures. These studies indicate that IL-11 belongs to a group of early-acting hematopoietic synergistic factors that now includes IL-6, G-CSF, and IL-11. In contrast, SF is unique among the synergistic factors in that it interacts either with growth factors such as IL-3 or GM-CSF or with synergistic factors such as IL-6, IL-11, or G-CSF.
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PMID:Enhancement of murine hematopoiesis by synergistic interactions between steel factor (ligand for c-kit), interleukin-11, and other early acting factors in culture. 137 16

The myelorestorative effects of granulocyte colony-stimulating factor (G-CSF), interleukin-1 alpha (IL-1 alpha) and interleukin-6 (IL-6) were studied in F-344 rats which had been treated with cyclophosphamide (CY), carboplatin (CBDCA), or nimustine hydrochloride (ACNU). In CY- or CBDCA-pretreated rats, significantly higher peripheral white blood cell (WBC) count was observed in animals treated with G-CSF and IL-1 alpha, while the platelet (PLT) count was elevated by IL-6 treatment. All of the cytokines had little effect on the hemoglobin (HB) value. Animals treated with ACNU had prolonged myelosuppression. Treatment of these animals with G-CSF and IL-1 alpha significantly enhanced the recovery of HB value as well as WBC count. Higher PLT counts were observed in treated groups, but a statistical difference was not evident. Combination therapy with G-CSF and IL-1 alpha, G-CSF and IL-6, or IL-1 alpha and IL-6 did not have any significant beneficial effects on the peripheral blood cell count in ACNU-pretreated rats over single agent therapy. Conversely, the combination of IL-6 and G-CSF had an unfavorable effect on HB and PLT levels. In rats which received multiple doses of ACNU, G-CSF treatment exhibited a beneficial effect on WBC, HB, and PLT levels, the most prominent on the HB value. These findings suggest that treatment with hematopoietic cytokines may be most beneficial when combined with anticancer drugs which are known to cause prolonged myelosuppression.
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PMID:Effects of granulocyte colony-stimulating factor, interleukin-1 alpha, and interleukin-6 on prolonged myelosuppression induced by nimustine hydrochloride in rats. 138 Feb 97

We examined the role of various hemopoietic factors in the survival of hemopoietic stem cells in methylcellulose culture. Bone marrow cells from 5-fluorouracil (5-FU)-treated mice were cultured without hemopoietic factors. Several days later, a mixture of colony-stimulating factors (CSF interleukin-3 (IL-3), interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF), and erythropoietin (Ep)) was added to the culture (delayed addition of CSF) to induce the maximal colony growth in surviving progenitors. In this system few colonies grew, suggesting that some hemopoietic factors are required for the survival of hemopoietic stem cells in vitro. In a further series of experiments, similar cultures were initiated with single known hemopoietic factors or with a mixture of CSF, followed by the addition of CSF 7 days later. Although IL-3 and G-CSF, as single factors, supported colony growth, the other factors did not. In this experiment, while the total number of colonies in cultures initiated with IL-3 or G-CSF was less than that observed in cultures initiated with a mixture of CSF, the number of multipotential GEMM (granulocyte-erythrocyte-macrophage-megakaryocyte) colonies remained constant. We concluded that IL-3 and G-CSF played important roles as single factors in the survival of murine dormant hemopoietic stem cells in vitro.
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PMID:Interleukin-3 and granulocyte colony-stimulating factor as survival factors in murine hemopoietic stem cells in vitro. 138 Aug 44

Transforming growth factor-beta 1 (TGF-beta 1) induces cell death in myeloid leukemia by apoptosis. In the M1 myeloid leukemia, this induction of apoptosis was inhibited by granulocyte colony-stimulating factor (G-CSF) or interleukin-6 (IL-6) and to a lesser extent by IL-1 alpha. IL-3 and stem cell factor/mast cell growth factor (SCF) showed only a marginal effect, and granulocyte-macrophage and macrophage CSFs (GM-CSF and M-CSF, respectively) were inactive. The induction of apoptosis by TGF-beta 1 in a different myeloid leukemia (7-M12) was inhibited by GM-CSF and IL-3 but not by the other cytokines. In the absence of TGF-beta 1, both M1 and 7-M12 leukemic cells were independent of hematopoietic cytokines for cell viability and growth. The cytotoxic compounds vincristine, vinblastine, adriamycin, cytosine arabinoside, cycloheximide, and sodium azide, some of which are used in cancer chemotherapy, induced cell death by apoptosis in both leukemias. As with TGF-beta 1, apoptosis induced by these cytotoxic compounds was inhibited by GM-CSF (7-M12 leukemia) and by G-CSF or IL-6 (M1 leukemia). Cyclosporine A decreased cell multiplication in M1 cells without inducing apoptosis, and G-CSF and IL-6 inhibited the cytostatic effect of cyclosporine A. It is suggested that the clinical use of cytokines to correct therapy-associated myelosuppression should be carefully timed to avoid protection of malignant cells from the cytotoxic action of the therapeutic compounds.
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PMID:Hematopoietic cytokines inhibit apoptosis induced by transforming growth factor beta 1 and cancer chemotherapy compounds in myeloid leukemic cells. 138 3

In previous reports we described our approach to the cultivation of murine and human thymic epithelial cells in primary cultures, using defined, serum-free growth factor-supplemented medium and extracellular matrix-coated culture plates. The cells in these cultures displayed high metabolic activity and their supernatant was highly active on thymocytes. In the study reported here we analysed cytokine activities in the supernatant of human thymic epithelial cell cultures (HTES), by using the respective cytokine-dependent cell lines and by neutralization with specific monoclonal antibodies. Three cytokine activities were detected--interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and macrophage (M)-CSF. Other cytokine activities tested for [IL-1, IL-2, IL-7, interferon (IFN) and tumour necrosis factor (TNF)] were negative. The effect of HTES on concanavalin A (Con A)-induced proliferation of murine thymocytes could be completely abolished by anti-IL-6 antibodies, but not by antibodies to CSF, whereas enhancement of bone marrow cell proliferation by HTES was partially inhibited by either anti-G-CSF or anti-M-CSF antibodies and completely inhibited by both antibodies, but not at all by anti-IL-6. We can thus distinguish between thymocyte-related cytokines (IL-6) and bone marrow (myeloid/monocyte) related ones (G-CSF, M-CSF) in HTES.
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PMID:Analysis of thymic stromal cell subpopulations grown in vitro on extracellular matrix in defined medium. IV. Cytokines secreted by human thymic epithelial cells in culture and their activities on murine thymocytes and bone marrow cells. 138 12


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