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)

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

We have previously shown that the synthetic tetraacyl precursor Ia (compound 406, LA-14-PP, or lipid IVa) was not able to induce the production of tumor necrosis factor, interleukin-1, and interleukin-6 in human monocytes but strongly antagonized lipopolysaccharide (LPS)-induced formation of these monokines. This inhibition was detectable at the level of mRNA production. To achieve a better understanding of molecular basis of this inhibition, we investigated whether lipid A precursor Ia (LA-14-PP), Escherichia coli-type lipid A (LA-15-PP), Chromobacterium violaceum-type lipid A (LA-22-PP), and synthetic lipid A partial structures and analogs (LA-23-PP, LA-24-PP, and PE-4) were able to influence the binding of 125I-LPS to human monocytes and compared this inhibitory activity with the agonistic and antagonistic action in the induction of monokines in human monocytes. 125I-LPS (20 ng per well) was added to human monocytes in the presence or absence of unlabeled rough Re mutant-derived LPS (Re-LPS) or lipid A compounds, and specific LPS binding was determined after 7 h. This binding was found to be dependent on CD14 as shown by the use of an anti-CD14 monoclonal antibody. Compound LA-14-PP was found to inhibit the binding of 125I-LPS to the cells in a similar dose-response to that of unlabeled LPS. This shows that the inhibitory capacity on LPS binding does not correlate with the monokine-inducing capacity because Re-LPS is active in inducing tumor necrosis factor, interleukin-1, and interleukin-6, while LA-14-PP is not. The strong capacity of LA-14-PP to inhibit 125I-LPS binding, however, correlates with the strong inhibitory capacity of this compound on LPS-induced monokine production. Compounds LA-15-PP, LA-23-PP, and LA-24-PP were active in the inhibition of 125I-LPS binding but were 5- to 10-fold weaker than Re-LPS and LA-14-PP. Of all lipid A structures tested, compound LA-22-PP expressed the weakest inhibitory capacity on LPS binding. These compounds showed again that the activity of binding inhibition does not correlate with the monokine-inducing capacity. We assume that the inhibitory effects of lipid A partial structures on LPS-induced monokine production have their origin in a competitive inhibition between LPS and the lipid A partial structures for the same binding site on the cell membrane.
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PMID:Modulation of endotoxin-induced monokine release in human monocytes by lipid A partial structures that inhibit binding of 125I-lipopolysaccharide. 128 Jun 25

The effects of interleukin-3 (IL-3) and interleukin-6 (IL-6) on nonadherent mononuclear cells (NMC) from the peripheral blood of 28 patients with multiple myeloma (MM), 3 patients with monoclonal gammopathy of undetermined significance (MGUS), and 3 normal controls were investigated. In 15 of 27 evaluable patients with MM, monoclonal-cytoplasmic-immunoglobulin (cIg)-positive plasma cells appeared from the T-cell-depleted NMC after 10 days of culture in the presence of IL-3 and IL-6. These changes were not observed in the T cell fraction of myeloma blood or in the T-cell-depleted NMC obtained from cases of MGUS or from normal controls. The percentage of cIg-positive plasmacytoid cells after 10 days of culture was significantly higher in the presence of both IL-3 and IL-6 than with each interleukin alone or the control medium. Furthermore, these changes were often observed in untreated patients. These findings suggest that myeloma precursor cells exist in the peripheral blood of MM patients, especially at diagnosis, and differentiate into cIg-positive cells in the presence of IL-3 and IL-6. This assay may be useful in discriminating the early stage of myeloma from MGUS.
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PMID:Effects of interleukin-3 and interleukin-6 on peripheral blood cells from multiple myeloma patients and their clinical significance. 128 99

c-kit is expressed on hematopoietic stem cells and progenitor cells, but not on lymphohematopoietic differentiated cells. Lineage marker-negative, c-kit-positive (Lin-c-kit+) bone marrow cells were fractionated by means of Ly6A/E or Sca-1 expression. Lin-c-kit+Sca-1+ cells, which consisted of 0.08% of bone marrow nucleated cells, did not contain day-8 colony-forming units-spleen (CFU-S), but 80% were day-12 CFU-S. One hundred cells rescued the lethally irradiated mice and reconstituted hematopoiesis. On the other hand, 2 x 10(3) of Lin-c-kit+Sca-1- cells formed 20 day-8 and 11 day-12 spleen colonies, but they could not rescue the lethally irradiated mice. These data indicate that Lin-c-kit+Sca-1+ cells are primitive hematopoietic stem cells and that Sca-1-cells do not contain stem cells that reconstitute hematopoiesis. Lin-c-kit+Sca-1+ cells formed no colonies in the presence of stem cell factor (SCF) or interleukin-6 (IL-6), and only 10% of them formed colonies in the presence of IL-3. However, approximately 50% of them formed large colonies in the presence of IL-3, IL-6, and SCF. Moreover, when single cells were deposited into culture medium by fluorescence-activated cell sorter clone sorting system, 40% of them proliferated on a stromal cell line (PA-6) and proliferated for more than 2 weeks. In contrast, 15% of the Lin-c-kit+Sca-1-cells formed colonies in the presence of IL-3, but no synergistic effects were observed in combination with SCF plus IL-6 and/or IL-3. Approximately 10% proliferated on PA-6, but most of them degenerated within 2 weeks. The population ratio of c-kit+Sca-1+ to c-kit+Sca-1- increased 2 and 4 days after exposure to 5-fluorouracil (5-FU). These results are consistent with the relative enrichment of highly proliferative colony-forming cells by 5-FU. These data show that, although c-kit is found both on the primitive hematopoietic stem cells and progenitors, Sca-1+ cells are more primitive and respond better than Sca-1- cells to a combination of hematopoietic factors, including SCF and stromal cells.
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PMID:In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells. 128 87

During inflammatory states, hepatocytes are induced to synthesize and secrete a group of proteins called acute-phase proteins. It has recently been shown that besides interleukin-6 (IL-6), related cytokines such as leukemia inhibitory factor, oncostation M and interleukin-11 are also mediators of the hepatic acute-phase response. All these mediators belong to the hematopoietic family of alpha-helical cytokines. Here we show that an additional member of this cytokine family, ciliary neurotrophic factor (CNTF), induces the hepatic acute-phase protein genes haptoglobin, alpha 1-antichymotrypsin, alpha 2-macroglobulin and beta-fibrinogen in human hepatoma cells (HepG2) and in primary rat hepatocytes with a time course and dose-response comparable with that of IL-6. Our next aim was to define the receptor components used by CNTF on hepatic cells. Using a cell-free binding assay we exclude that CNTF binds to the 80 kDa IL-6 receptor, a protein with significant homology to the CNTF receptor which has recently been cloned from neuroblastoma cells. In human hepatoma cells (Hep3B) which lack the leukemia inhibitory factor receptor, CNTF was not able to induce acute-phase protein synthesis, indicating that this receptor protein may be part of the functional CNTF receptor on hepatic cells.
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PMID:Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes. 128 89

Messenger RNAs and proteins of scavenger receptor thought to be macrophage specific protein were expressed in renal cell carcinoma (RCC) cells in vitro. Acetyl LDL was taken up into RCC cells and promoted the production of interleukin-6 (IL-6), an in vitro autocrine growth factor to proliferate the cells. These results suggested that RCC cells might have a scavenger pathway which has not yet been demonstrated except for macrophages.
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PMID:Expression of scavenger receptors on renal cell carcinoma cells in vitro. 128 99

1. Rats established on a normal (20% protein) diet or a protein-deficient (3% protein) diet were given either a subcutaneous injection of turpentine (5 ml/kg), which induces formation of aseptic abscesses, or saline. Plasma samples were obtained at timed intervals (0-14 days) after the injection for determination of albumin, total protein, alpha 2-macroglobulin (a major acute-phase protein in the rat) and interleukin-6 concentrations. The magnitude and pattern of the acute-phase protein response was then compared with the local inflammatory reaction, assessed histologically, and with changes in the circulating concentration of interleukin-6, which is an important mediator of the acute-phase protein response. 2. After turpentine injection there was an early fall in the plasma albumin and total protein concentrations in both normal and protein-deficient rats. After 12 h the total protein concentration increased in both groups of animals reaching a peak at about 48 h, whereas the plasma albumin concentration continued to fall reaching a minimum at 48 h. The main alpha 2-macroglobulin response was delayed and attenuated in the protein-deficient rats (onset 9 versus 24 h, peak concentration 8.95 +/- 0.5 versus 5.33 +/- 0.75 g/l, P < 0.01, and area under the concentration-time curve 18.43 +/- 2.13 versus 7.96 +/- 1.48 g/l-1 days, P < 0.01, in the normal group and protein-deficient group, respectively). 3. The circulating interleukin-6 concentration showed a transient early rise at 1 h, and was followed by a larger more sustained peak at 6-48 h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of aseptic abscesses in protein-deficient rats on the relationship between interleukin-6 and the acute-phase protein, alpha 2-macroglobulin. 128 54

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 vitro models have shown that interleukin-6 (IL-6) is the main dominator of the stimulation of the full spectrum of acute phase proteins. This study describes IL-6 levels in relation to levels of acute phase proteins in 15 systemic lupus erythematosus (SLE) patients, with special attention given to those patients with increased serum levels of IL-6. Three episodes with elevated levels of IL-6 were observed in a period shortly after a flare-up of SLE, in three of the 15 patients. In one of these three patients a clear increase in the C-reactive protein (CRP) level, preceded by an IL-6 increase, was observed. In the other two patients, CRP levels remained unchanged. It is speculated that, next to IL-6, another signal is operative or needed for the start of an acute phase reaction. However, influences of the disease itself or of the administered therapy cannot be excluded as the cause of the described discrepancy between IL-6 and acute phase protein profiles in these two SLE patients.
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PMID:Observations on the interleukin-6 and acute phase protein profiles in the disease course of patients with lupus erythematosus. 128 44

A case of 44-year-old woman who had shown psychiatric symptoms before and during the course of Castlemans' disease was presented. For four years, she first suffered from a paranoid-hallucinatory state and then a depressive one episodically. In the course of the latter, severe anemia developed. She was diagnosed as Castleman's disease, because the increased serum level of gamma-globulin and interleukin-6 (IL-6), and multiple lymphomata were evidenced. A paranoid-hallucinatory state relapsed about one year later from this episode. At last, some bulbar and cerebellar symptoms, and a delirium suddenly occurred. The ischemic changes at the level of the pons and midbrain were revealed by the magnetic resonance imaging (MRI) examination. It is certainly that both neurological and psychiatric symptoms were related to the lesions. This ischemic lesions may have resulted from the anoxia secondary to the severe anemia and/or hyperviscosity syndrome in the disease. On the other hand, the increased serum level of IL-6 as well as the ischemic lesions might have caused psychiatric symptoms in this case, as the interferone which is one of the analogues of IL-6, is known to induce emotional and behavioral symptoms.
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PMID:[A case of Castleman's disease with a variable neuropsychiatric symptomatology]. 128 94


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