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)

The growth-promoting activities of optimally stimulating concentrations of leukemia inhibitory factor (LIF) and interleukin-11 (IL-11), a stromal cell-derived cytokine, on megakaryocytes in liquid marrow cultures were compared to interleukin-6 (IL-6), a known megakaryocytes maturation factor. Maximally stimulating concentrations of LIF (25 ng/ml), IL-11 (10 ng/ml), or IL-6 alone (10 ng/ml) promoted an 81, 157, and 153% increase, respectively, in acetylcholinesterase (AchE) activity in murine serum-free cultures compared with controls (n = 5). In combination with 25 U/ml murine interleukin-3 (IL-3), LIF, IL-6, and IL-11 showed increases, respectively, of 35%, 49%, and 174% in AchE activity compared with IL-3 alone (n = 4). Flow cytometric analysis of 4-day-old cultures showed that LIF alone had minimal effect on megakaryocytic ploidy, whereas IL-11 and IL-6 alone markedly augmented high ploidy cells. Enumeration of cells stained for AchE showed that IL-11 increased the numbers of Mks in comparison to LIF, IL-6 or controls by up to 59%. Moreover, a twofold increment in Mk number was noted when IL-11 was used in combination with IL-3 (compared with either IL-3 alone of IL-3+IL-6). Flow cytometric ploidy analysis of 8-day-old human liquid marrow cultures showed that either LIF, IL-11, or IL-6 alone markedly augmented the percentage of 32N cells compared with cultures containing only human IL-3. The data suggest that LIF and IL-11 promote murine and human Mk maturation in vitro, although the effect of IL-11 exceeds that of LIF in mice. Despite the comparable influence of IL-11 and IL-6 on Mk ploidy, IL-11 has the additional characteristic of enhancing the number of Mks, particularly in combination with IL-3.
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PMID:Leukemia inhibitory factor and interleukin-11 promote maturation of murine and human megakaryocytes in vitro. 142 51

Interleukin-6 (IL-6) and leukemia inhibitory factor (LIF) promoted the survival of acetylcholinesterase (AChE)-positive neurons in culture from embryonic E15 rat spinal cord. Half of the AChE-positive neurons died during 3-7 days in culture in the absence of IL-6 and LIF. However, IL-6 at a concentration of 5 ng/ml completely prevented the death of AChE-positive neurons. LIF at a concentration of 5 U/ml also stimulated the survival of neurons, although to a lesser extent than IL-6. IL-6 and LIF also increased the numbers of process-bearing neuron-like cells in culture. The dose-dependencies of IL-6 and LIF with regard to the survival of total neuron-like cells were different from those for AChE-positive neurons.
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PMID:Interleukin-6 and leukemia inhibitory factor promote the survival of acetylcholinesterase-positive neurons in culture from embryonic rat spinal cord. 143 52

Thrombopoietin or thrombocytopoiesis-stimulating factor (TSF) is known to be the natural stimulator of megakaryocytopoiesis and, thus, stimulates thrombocytopoiesis. In the past 15 years, new assay technology and sources of the hormone have made possible partial characterization of the molecule and clarification of the biologic role of thrombopoietin. Experiments describing the biology and characterization of TSF are reviewed. In addition, a brief history of the molecule, its biology, and the effects of thrombopoietin on both thrombocytopoiesis and megakaryocytopoiesis are discussed, including the effects of thrombopoietin on platelet counts, platelet sizes, and incorporation of isotopes. In the discussion of thrombopoietin's control of megakaryocytopoiesis there is specific information showing that thrombopoietin stimulates an increase in megakaryocyte size and number, DNA content, endomitosis, and maturation. Thrombopoietin also increases the number of early precursor cells of the megakaryocytic series, that is, small acetyl-cholinesterase-positive cells. New information is given on the chemistry of thrombopoietin, along with present assays and the relationship of thrombopoietin to interleukin-6. The clinical aspects of thrombopoietin, with detailed descriptions of several disease states in which decreases and excesses of the hormone have been found, are presented. The potential uses of thrombopoietin in clinical medicine are reviewed. In the near future, it appears that successful gene cloning of the hormone will be achieved, which will allow production of large amounts of recombinant thrombopoietin. The pure material will be helpful in clarifying the hormone's mode of action. Thrombopoietin will no doubt prove to be useful in treating patients with various hematologic disorders, such as patients undergoing bone marrow transplantation, chemotherapy, or radiotherapy, and other patients with various types of marrow hypoplasia.
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PMID:Thrombopoietin. Its biology, clinical aspects, and possibilities. 155 Feb 68

Megakaryocytic maturation was analyzed in long-term bone marrow cultures in the absence of added growth factors. Megakaryocytes could be observed for periods of up to 13 weeks in both the supernatant and stromal layer of these cultures. Using acetylcholinesterase staining for enumeration and sizing of megakaryocytes, and a novel rat antimurine platelet monoclonal antibody (MoAb) that detects only megakaryocytes in bone marrow, the number, volume, and ploidy of these cells were assessed microscopically and by flow cytometry. Correlation of these measurements with ambient interleukin-6 (IL-6) levels showed no relationship between IL-6 bioactivity and megakaryocyte number. Conversely, the relatively high IL-6 bioactivity present during the first 2 weeks of culture was correlated with increased megakaryocytic size and ploidy, while the relatively lower IL-6 bioactivity present after week 3 corresponded to decreased megakaryocytic size and ploidy. Addition of neutralizing anti-IL-6 MoAb decreased megakaryocytic size and ploidy at times when ambient IL-6 levels were relatively high, while the addition of exogenous IL-6 increased size and ploidy at times when endogenous IL-6 concentrations were low. The data show that long-term bone marrow cultures can be used as a means to evaluate megakaryocytic maturation in vitro, and suggest that, to some extent, IL-6 plays a role in the maturation process in this system.
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PMID:Megakaryocytic maturation in murine long-term bone marrow culture: role of interleukin-6. 183 56

A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) derived from human embryonic kidney (HEK) cells is known to increase platelet production and to increase the number of morphologically unrecognizable early megakaryocytes, ie, small acetylcholinesterase-positive (SAChE+) cells in mice. Other recent studies have concluded that interleukin-6 (IL-6) also stimulates murine megakaryocytopoiesis both in vitro and in vivo. Some workers have suggested that IL-6 is thrombopoietin. Therefore, the purpose of this study was to compare the effects of TSF and IL-6 on percent 35S incorporation into platelets, platelet sizes, and the percentages of SAChE+ cells in C3H mice, and to determine if they produce the same or different responses. The results showed that two or four injections of a partially purified TSF (total dose of 2 or 4 units (U) over a 1- or 2-day period) increased percent 35S incorporation into platelets (P less than .005) and platelet sizes (P less than .005) of both normal and rebound-thrombocytotic mice when compared with values from other mice treated with human serum albumin, the carrier protein for both TSF and IL-6. In eight separate experiments, it was shown that IL-6 (40,000 U, 4 micrograms), when given to rebound-thrombocytotic mice in four injections over a 2-day period, produced a small but significant (P less than .005) increase in percent 35S incorporation into platelets. Additional studies showed that negative results were obtained when similar high doses of IL-6 were administered in two doses over a 1-day period. TSF, but not IL-6, stimulated an increase in platelet sizes of normal mice (P less than .005 to 0.0005); however, IL-6 increased platelet sizes of rebound-thrombocytotic mice when given in two of four injections (P less than .05 to .0005). Also, IL-6, but not TSF, caused anemia in normal mice (P less than .0005) that were given two injections and tested 3 days later. TSF stimulated an increase (P less than .005) in the percentage of SA-ChE+ cells; whereas IL-6, even at high doses, did not. Because of the observed differences in biologic responses of these two cytokines, we conclude that TSF and IL-6 are separate entities.
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PMID:Comparative effects of thrombopoietin and interleukin-6 on murine megakaryocytopoiesis and platelet production. 199 16

Interleukin-6 (human recombinant) supported the survival of cultured mesencephalic, catecholaminergic and septal cholinergic neurons from postnatal, two-week-old (P13-P15) rats. Significantly, more catecholaminergic neurons, stained by monoclonal anti-tyrosine hydroxylase antibody, were found in cultures supplemented with interleukin-6 at a concentration of 5 ng/ml than in cultures not treated with interleukin-6. The optimal dose used was 50 ng/ml. The survival effect of interleukin-6 on postnatal rat, tyrosine hydroxylase-positive neurons was observed both in cultures using serum-containing and serum-free medium. Contents of dopamine and noradrenaline in cultures with interleukin-6 were also larger than in control cultures. Interleukin-6 also increased the survival of cultured embryonic (E17) rat midbrain tyrosine hydroxylase-positive neurons. The effect on these neurons was, however, smaller, and the optimal dose of interleukin-6 was nearly 5 ng/ml. Interleukin-6 also supported the survival of cultured postnatal (P13) rat septal cholinergic neurons, visualized by acetylcholinesterase staining. The concomitant addition of mouse nerve growth factor (100 ng/ml) and interleukin-6 (50 ng/ml) had a synergetic effect on the survival of acetylcholinesterase-positive neurons in culture. Our data suggest that the survival of cultured tyrosine hydroxylase-positive, mesencephalic, and acetylcholinesterase-positive, septal neurons from postnatal two-week-old rats was supported by interleukin-6, just as there was a different dose dependency of interleukin-6 on the cultured postnatal neurons compared with embryonic neurons.
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PMID:Interleukin-6 improves the survival of mesencephalic catecholaminergic and septal cholinergic neurons from postnatal, two-week-old rats in cultures. 202 69

Determinations of total cytokine concentration in biological fluids by immunoassays face two major problems: the biochemical heterogeneity of the analyte and the interference of cytokine-binding proteins. We developed an ultrasensitive enzyme immunoassay for interleukin-6 (IL-6), using monoclonal antibodies and acetylcholinesterase as the tracer enzyme. The antibodies recognized recombinant and glycosylated forms of IL-6 equally. The antibodies measured dimeric recombinant IL-6, yet we could not detect IL-6 oligomers in plasma samples. We investigated the potential interference of soluble IL-6 receptor (sIL-6R), which is present at high concentrations in plasma samples (1 to 2 nmol/L). Heat treatment of the sample obviated the sIL-6R interference. Using calibrators in a plasma matrix, we demonstrated by fractionation, dilution, and recovery experiments that the immunoassay accurately measured total IL-6 in both normal and pathological serum and plasma samples.
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PMID:Total interleukin-6 in plasma measured by immunoassay. 828 18

Mouse megakaryocytes were purified using a rabbit antimouse platelet serum, and magnetic beads were conjugated with an antirabbit IgG antibody. The purified cells were 95.8 +/- 1.2% megakaryocytes, and the recovery and viability of the megakaryocytes were 70 +/- 18.4%, and 80 +/- 13.4%, respectively. The effects of recombinant erythropoietin (Epo), interleukin-6 (IL-6), and IL-1 beta on these purified megakaryocytes were studied. Epo and IL-6 significantly increased DNA synthesis in these cells, but IL-1 beta did not. Similarly, both Epo and IL-6, but not IL-1 beta, increased the acetylcholinesterase (AchE) activity in the megakaryocytes. Epo and IL-6 stimulated the megakaryocytes to form cytoplasmic processes, which are considered to represent in vitro proplatelet formation. This process formation was inhibited by the addition of colchicine to the cultures. It was concluded that Epo and IL-6 are not only direct potentiators of megakaryocytes, but also inducers of in vitro cytoplasmic process formation on megakaryocytes.
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PMID:Interleukin-6 and erythropoietin act as direct potentiators and inducers of in vitro cytoplasmic process formation on purified mouse megakaryocytes. 829 37

Studies were performed to investigate the relationship between serum interleukin-6 (IL-6) and the nutritional status in chronic hemodialysis patients. Serum IL-6 in 45 patients (21 men and 24 women), each with chronic renal failure and having undergone hemodialysis for more than 3 years, was measured before and after a dialysis session. The nutritional status of each patient was evaluated by measuring body mass index (BMI), body weight loss for 3 years, midarm muscle area (MAMA), serum albumin, prealbumin, and insulin-like growth factor-1. Serum IL-6 was significantly higher in the patients undergoing hemodialysis (11.7 +/- 2.8 pg/mL) than in healthy volunteers (< 0.6 pg/mL). There was no further increase in serum IL-6 after a dialysis session when the extracellular water volume was corrected by the ultrafiltrate volume. Predialytic serum IL-6 was significantly correlated with serum albumin (r = -0.4, P = 0.006), cholinesterase (r = -0.51, P = 0.001), body weight change for 3 years (r = -0.48, P = 0.001) and MAMA r = -0.39, P = 0.05). With the patients divided into two groups, a high serum IL-6 (>10 pg/mL) group and low serum IL-6 (<10 pg/mL) group, the body weight loss for 3 years (-4.60% +/- 1.39% v 0.76 +/- 0.75%, P < 0.01) was significantly higher, and the serum albumin level (3.66 +/- 0.10 g/dL v 3.96 +/- 0.05 g/dL, P < 0.05) was significantly lower in those patients with high serum IL-6 than in those with low serum IL-6. The results of a multiple regression analysis indicated that the serum IL-6 level was dependent on the duration of hemodialysis, age, and the dialysis membrane properties. These results suggest that the nutritional status in chronic hemodialysis patients was affected, at least in part, by the circulating IL-6 level. Multiple factors, such as long-term hemodialysis, aging, and the use of a regenerated cellulose membrane dialyzer, were associated with this increased level of IL-6.
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PMID:Interleukin-6 may mediate malnutrition in chronic hemodialysis patients. 942 58

Oral exposure to chlorpyrifos (CHP) in the rat results in an initial hypothermic response followed by a delayed fever. Fever from infection is mediated by the release of cytokines, including interleukin-6 (IL-6) and tumor necrosis factor (TNF alpha). This study determined if the CHP-induced fever involves cytokine-mediated mechanisms similar to that of infectious fevers. Long-Evans rats were gavaged with the corn oil vehicle or CHP (10-50 mg/kg). The rats were euthanized and blood collected at various times that corresponded with the hypothermic and febrile effects of CHP. Plasma IL-6, TNF alpha, cholinesterase activity (ChE), total iron, unsaturated iron binding capacity (UIBC), and zinc were measured. ChE activity was reduced by approximately 50% 4 h after CHP. There was no effect of CHP on IL-6 when measured during the period of CHP-induced hypothermia or fever. TNF alpha levels nearly doubled in female rats 48 h after 25 mg/kg CHP. The changes in plasma cytokine levels following CHP were relatively small when compared to > 1000-fold increase in IL-6 and > 10-fold rise in TNF alpha following lipopolysaccharide (E. coli; 50 microg/kg; i.p.)-induced fever. This does not preclude a role of cytokines in CHP-induced fever. Nonetheless, the data suggest that the delayed fever from CHP is unique, involving mechanisms other than TNF alpha and IL-6 release into the circulation characteristic of infectious fevers.
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PMID:Are circulating cytokines interleukin-6 and tumor necrosis factor alpha involved in chlorpyrifos-induced fever? 1041 84


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