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)

In the present report, we show that progressive growth of the immunogenic C57BL/6J sarcoma, MCA/76-9, was accompanied by an increase in serum interleukin-6 (IL-6) activity. The possible pathways leading to the induction of IL-6 release by the tumor cells are described. It was shown that macrophage products IL-1 alpha, IL-1 beta, and to a lesser extent, TNF alpha, induced the tumor cells in vitro to transcribe the IL-6 gene and release the gene product. IL-1 induced significantly more IL-6 mRNA and bioactivity than TNF alpha, although both cytokines induced a cumulative increase of bioactivity in the supernates over a period of 24 h. The tumor cells were shown to express receptors for IL-1 alpha, which could be blocked with anti-IL-1 receptor antibody. Given the previous reports that tumor-associated macrophages expressed both IL-1 alpha/beta and TNF alpha, the data suggest, first, that the mutual interaction of tumor cells and macrophages in situ may contribute to the observed increase in circulating IL-6 activity, and second, that the release of IL-6 in vivo may serve to regulate both anti-tumor immune responses and suppressor mechanisms.
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PMID:Tumor cell IL-6 gene expression is regulated by IL-1 alpha/beta and TNF alpha: proposed feedback mechanisms induced by the interaction of tumor cells and macrophages. 140 92

Interleukin-1(IL-1), a cytokine present in the gingiva and crevicular fluid of patients with periodontitis and in the periodontal ligament (PDL) of experimentally moved teeth, has multiple biological activities, including the ability to elicit bone resorption. Interleukin-6, also found in the gingiva of patients with periodontitis, may induce osteoclastic bone resorption through an effect on osteoclastogenesis. Here IL-6 production and its gene expression in response to recombinant IL-1 beta were examined in primary cultures of PDL cells. IL-1 beta stimulated IL-6 production by these cells in a dose- and time-dependent manner; this increase in IL-6 production was much higher than that in human gingival fibroblasts. In situ hybridization, using a synthetic oligonucleotide DNA probe of the IL-6 gene, revealed that most PDL cells expressed IL-6 mRNA in response to IL-1 beta treatment. The finding that IL-6 is produced by PDL cells and is regulated by IL-1 beta has revealed a potentially important mechanism for controlling alveolar bone resorption.
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PMID:Stimulation by interleukin-1 of interleukin-6 production by human periodontal ligament cells. 141 23

Studies on the structure of haemopoiesis in acute myeloblastic leukaemia (AML) has shown the presence of a small population of malignant cells with extensive proliferative and self-renewal properties which are features of stem cells. The requirements of these cells for proliferation have been studied both in clonogenic assays in semi-solid media and in liquid suspension culture. These have demonstrated that AML clonogenic cells from the majority of patients, can be stimulated to proliferate by colony-stimulating factors (GM-CSF, G-CSF and IL-3) as well as other cytokines including interleukin-1 and interleukin-6, all of which are known to stimulate normal haemopoietic progenitors. Unlike normal haemopoietic cells, leukaemic blasts from many patients with AML express transcripts for haemopoietic growth factors including GM-CSF, G-CSF and IL-1 but not IL-3, and secrete growth factor protein. When leukaemic cells are cultured at sufficiently high density to permit cell-cell interactions, autonomous growth of clonogenic cells can be seen. Autonomous growth is related to the autocrine secretion of haemopoietic growth factors including GM-CSF, G-CSF and IL-6. The degree of autonomous colony growth is variable but approximately 70% of AML samples exhibit either partial or totally autonomous growth; the remaining cells being absolutely dependent on exogenous CSF or fail to grow in the culture systems employed. Similar patterns of growth have been found in murine haemopoietic cells lines which have been transformed as the result of the retroviral insertion of genes for GM-CSF or IL-3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Autocrine growth factors and leukaemic haemopoiesis. 142 83

Mycoplasma arthritidis produces a so-far only partially characterized soluble material (MAS) that has a potent mitogenic effect on T lymphocytes of several species. Similar to staphylococcal enterotoxins and a number of related toxins secreted by other species of bacteria, nanogram quantities of these so-called superantigens are sufficient to induce significant amounts of cytokines in the supernatant of lymphocyte cultures. Induction of interleukin-6 (IL-6) by MAS in murine bone marrow-derived macrophages has recently been described. In our study, we examined the differential effects of MAS and Staphylococcus aureus enterotoxin B (SEB) on human blood cells. When compared to MAS, SEB induced a higher proliferative response and, accordingly, a higher release of IFN-gamma. In contrast, large amounts of the macrophage products IL-1, IL-6 and tumor necrosis factor alpha (TNF-alpha) were observed in supernatants of cell cultures stimulated with MAS, whereas only small amounts were induced by SEB. Staphylococci and mycoplasmas are responsible for a number of diseases with various symptoms in man and animals. Our results suggest that SEB and MAS show different qualities in lymphocyte and macrophage stimulation which may be relevant in the pathogenesis of diseases.
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PMID:Induction of cytokines in human whole blood cultures by a mitogen derived from Mycoplasma arthritidis and by staphylococcal enterotoxin B. 149 Jul 30

Astrocytes and microglia, both produced interleukin-6 (IL-6) in culture by lipopolysaccharide (LPS) stimulation. IL-6 activity was detected 3-5 h after LPS stimulation and reached a maximum at 10 h. Microglia responded faster than astrocytes. Tumor necrosis factor alpha and interleukin 1 also induced IL-6 mRNA and biological activity in astrocytes, but not in microglia. Among these stimuli, LPS was the most potent inducer of IL-6 production by astrocytes. Our results suggest that different regulatory mechanisms for cytokine production exist in glial cells. The possible roles of astrocytes and microglia in CNS immune responses are also discussed.
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PMID:TNF alpha induces IL-6 production by astrocytes but not by microglia. 150 36

The effect of induction of an acute-phase response and its mediators on the development of liver schizonts of the rodent malaria parasite Plasmodium berghei was investigated in Brown Norway rats. Subcutaneous injection of turpentine oil 24 h or 5 min before inoculation of sporozoites resulted in 80% and 35% reduction of schizont development, respectively. Turpentine oil induced high plasma levels of interleukin-6 (IL-6). Intraperitoneal administration of IL-1, IL-6 or both, significantly reduced liver schizont development. This reduction was also present if IL-6 had been administered 24 h after sporozoite inoculation. Inhibition induced by IL-1 could be prevented by simultaneous administration of polyclonal anti-IL-6. Administration of polyclonal anti-IL-6 without IL-1 resulted in a 40% increase of liver schizonts compared to control animals. We conclude that induction of an acute-phase response during experimental Plasmodium berghei infections in Brown Norway rats, strongly inhibits liver schizont development and that IL-6 is a key mediator in this process.
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PMID:Cytokines inhibit the development of liver schizonts of the malaria parasite Plasmodium berghei in vivo. 151 19

The anticoagulant used for the collection of blood was found to influence in vitro cytokine production in whole blood. Lithium heparin in certain collection tubes was found to contain endotoxin and induced cytokine synthesis in a time-dependent manner whereas endotoxin-free lithium heparin did not. No induction of cytokine occurred in the presence of EDTA which was also able to inhibit endotoxin-induced cytokine synthesis. Synthesis or absence of cytokine correlated with the induction of messenger RNA. Investigation of the kinetics of cytokine induction in whole blood revealed that tumour necrosis factor alpha (TNF) was detectable after 2 h of incubation at 37 degrees C and interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) after 3 h. In certain samples IL-1 and IL-6 were detectable in plasma separated immediately from blood collected into endotoxin-free lithium heparin, presumably reflecting in vivo synthesis, and similar concentrations were detected after 3 h of incubation of whole blood at 37 degrees C. These data indicate that as long as blood is collected into endotoxin-free anticoagulant then cytokine measurements will reflect the in vivo status.
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PMID:Influence of collection and separation of blood samples on plasma IL-1, IL-6 and TNF-alpha concentrations. 151 82

Like blood monocytes, the human monocytic cell line Mono Mac 6 can be stimulated by lipopolysaccharide (LPS) at 1 microgram/ml to produce high levels of cytokines. When Mono Mac 6 cells are stimulated for 4-6 hr at 1 x 10(6)/ml, supernatants contain tumour necrosis factor (TNF) at an average of 60 U/ml and interleukin-6 (IL-6) at an average of 1000 U/ml. IL-1 is not detected in the supernatant, but after three freeze-thaw cycles cell-associated IL-1 can be detected (100 U/ml) and with similar amounts of IL-alpha and -beta. Preculture of Mono Mac 6 cells with LPS at 10 ng/ml for 3 days results in cells refractory to subsequent stimulation by LPS at 1 microgram/ml. In the refractory desensitized cells, production of all three cytokines is down-regulated, with a more than 10-fold reduction in protein production. For all three cytokines, this desensitization appears to be regulated at the transcript level, with a strong reduction in specific mRNA as detected by Northern blot analysis. Furthermore, Mono Mac 6 cells can be stimulated by Staphylococcus aureus (LPS contamination less than 10 pg/ml) to produce cytokines. This type of stimulus is unable to overcome desensitization, in that the secretion of TNF in LPS-precultured Mono Mac 6 cells was 10- to 100-fold lower than in Mono Mac 6 cells without LPS preculture. These data show that desensitization in Mono Mac 6 cells affects all three cytokines tested and that it extends to other activating signals, such as staphylococci.
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PMID:In vitro desensitization to lipopolysaccharide suppresses tumour necrosis factor, interleukin-1 and interleukin-6 gene expression in a similar fashion. 155 89

We have demonstrated that centrally administered interleukin-6 (IL-6) stimulates adrenocorticotropin (ACTH) secretion by a direct effect on corticotropin-releasing factor (CRF) release from the hypothalamus. Since metabolites of the arachidonic acid cascade (AAC) have been implicated in mediating actions of cytokines in different tissues and some AAC inhibitors were able to block pyrogenic effects of cytokines and suppress IL-1-induced ACTH secretion, we decided to examine the mechanism of IL-6 action on CRF release in vitro. After a 60-min preincubation in Krebs-Ringer bicarbonate buffer, medial basal hypothalami (MBH) were preincubated for 30 min with dexamethasone (DEX), a phospholipase A2 (PLA2) inhibitor, to block arachidonic acid (AA) formation, or with inhibitors of AA metabolism: a cyclooxygenase inhibitor--indomethacin (IND); a lipoxygenase inhibitor--5,8,11-eicosatriynoic acid (ETI), and an epoxygenase inhibitor--clotrimazole (CLO). Then, the medium was discarded and MBH were incubated with medium or the above compounds and/or IL-6 for 30 min, and CRF release into the incubation medium was measured by radioimmunoassay. As reported previously, 10(-13) M IL-6 increased CRF release, which was significantly suppressed by DEX in a dose-dependent manner. The suppression was already highly significant at a concentration of 10(-11) M DEX and became maximal at 10(-7) M, at which concentration CRF release was no longer stimulated by IL-6. The response to IL-6 was completely blocked at the highest DEX concentration evaluated (10(-5) M). CLO also suppressed IL-6-induced CRF release with a minimal effective dose of 10(-9) M. Suppression was complete at 10(-7) and 10(-5) M.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of arachidonic acid cascade pathways in interleukin-6-stimulated corticotropin-releasing factor release in vitro. 163 May 86

This report was aimed at confirming the potential clinical use for a genetically engineered glycosylated human interleukin-6 (rhIL-6) in hematopoiesis. Its tolerance and efficacy were assessed on hematopoietic restoration after neutron radiation-induced bone marrow injury on baboons, which represent an adequate model of parallelism for studying hematology in the human. The particular neutron radiation absorption pattern in the body allows the preservation of underexposed bone marrow areas that mimics an autotransplantation-like situation. An initial dose finding study (1 microgram up to 20 micrograms/kg/d for 8 consecutive days) in normal baboons established a dose-dependent response regarding the peripheral platelet count (range of increase, 1.5- to 4-fold). A significant elevation in white blood cell (WBC) count, as well as a substantial reversible normochromic normocytic anemia, were observed for the highest doses only (10 and 20 micrograms/kg/d). All rhIL-6 administered doses were clinically well tolerated. In myelosuppressed baboons, a selected dose of 10 micrograms/kg/d of rhIL-6 for 13 consecutive days significantly lessened the degree of induced thrombocytopenia as compared with the control group (P = .01) and shortened the time to occurrence of the nadir, showing that the onset of recovery occurs much earlier, ie, an average of 5 days (P = .003), in the treated group. Moreover, this accelerated platelet recovery is evidenced by an 8-day shorter mean time back to baseline values (P = .03) in the rhIL-6--treated animals. At this dose no effect was observed on the WBC recovery pattern. Importantly rhIL-6 did not accentuate the radiation-induced anemia and was clinically well tolerated. All tested monkeys recovered from their induced pancytopenia and no animal loss was recorded. IL-6, tumor necrosis factor, and IL-1 blood measurements are reported. In conclusion, rhIL-6 is a potent thrombopoietic factor for the treatment of induced thrombocytopenia in nonhuman primates at a clinically well-tolerated dose.
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PMID:Recombinant glycosylated human interleukin-6 accelerates peripheral blood platelet count recovery in radiation-induced bone marrow depression in baboons. 163 22


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