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)

A protein purified from Eschericheri coli has previously been shown to have cytotoxic effects on neoplastic cells of several lineages both in vitro and in vivo. Accordingly, this protein has been named anti-neoplastic protein (ACP). Although ACP kills neoplastic cells by inducing apoptosis, it has negligible effects on various normal cells. In addition to the direct cytotoxic effects of ACP on tumour cells, previous studies have shown that in vivo ACP increases tumouricidal activity of cytotoxic lymphocytes. We investigated whether cytokines from host or tumour cells play a part in the enhanced cellular immunity seen in ACP-treated tumour-bearing mice. Growth of normal human keratinocytres (KC) was not significantly affected by subnanogram amounts of ACP, however ACP dose-dependently killed KHT cells, a murine fibrosarcoma cell line (LD50 = 8 x 10(4) ng/cell). as well as the human squamous carcinoma cell line COLO-16 (LD50 = 2.5 x 10(-4) ng/cell). Testing purified ACP on cultures of normal keratinocytes and squamous carcinoma cell lines revealed that ACP could induce both mRNA and protein for interleukin-6 (IL-6). Messenger RNA for IL-6 increased dose-dependently 4h after treatment of COLO-16 squamous carcinoma cells with 10(-4) to 10(-2) ng/cell ACP. Maximal increment was 50-fold. Interleukin-6 message remained elevated up to 24h later in both normal keratinocytes and squamous carcinoma cultures treated with ACP. Conditioned supernates from these cultures were analysed by ELISA and found to have 4-fold higher levels of IL-6 protein than untreated cells after 4h. After 24h, IL-6 did not increase above the 4h level. Boiling of the ACP preparation showed that the cytokine induction was not due to contaminating lipopolysaccharide. The cytoxic effect of ACP on tumour cells in vitro was not due to IL-6 protein induction since neither recombinant IL-6, nor the other proinflammatory cytokines, IL-1 alpha or Tumour necrosis factor-alpha (TNF-alpha) (0.1-10ng/ml) were able to kill malignant cells. We demonstrated IL-6 gene induction by ACP in the squamous carcinoma lines as well as in normal KC. This suggests that the in vivo effectiveness of ACP against tumours may be due to stimulatory effects of IL-6 on host immunity.
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PMID:Augmentation of interleukin-6 (IL-6) expression in squamous carcinoma cells and normal human keratinocytes treated with recombinant anti-neoplastic protein (ACP). 807 68

1. Cytokine production in vitro was assessed in 16 malnourished children, before and after nutritional recovery. 2. Tumour necrosis factor-alpha and interleukin-6 were measured in whole blood after lipopolysaccharide stimulation. 3. The total amount of both cytokines was significantly less after 24 h incubation among malnourished children when compared with the same children after nutritional rehabilitation. 4. Cytokine production in vitro is impaired in severely malnourished children.
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PMID:Production of interleukin-6 and tumour necrosis factor-alpha in vitro is reduced in whole blood of severely malnourished children. 815 45

Cytokines play a major role in the pathophysiology of septic shock. In this study, human peripheral blood monocytes were stimulated with peptidoglycan and teichoic acid, purified from a strain of Staphylococcus epidermidis. Polymyxin B (PM-B) was added to avoid the effects of possible contamination with endotoxin. Tumour necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), and interleukin-6 (IL-6) in the supernates were measured by enzyme-linked immunosorbent assays. Peptidoglycan and teichoic acid induced TNF, IL-1, and IL-6 in a concentration-dependent manner. Teichoic acid was a weaker inducer than peptidoglycan, especially for IL-1. Lipopolysaccharide from an E. coli strain was used as a control, being 100-1000 times more potent than peptidoglycan and teichoic acid.
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PMID:Peptidoglycan and teichoic acid from Staphylococcus epidermidis stimulate human monocytes to release tumour necrosis factor-alpha, interleukin-1 beta and interleukin-6. 827 59

Interleukin-6 (IL-6) was secreted by cultured cells of 7 out of 11 human pituitary adenomas that were examined. Interleukin-1 (IL-1) stimulated IL-6 release after a 24-h incubation period in five of the seven IL-6-secreting adenoma cultures and in all seven after 72 h. Tumour necrosis factor, interferon-gamma and epidermal growth factor did not significantly affect IL-6 secretion. Interleukin-1 failed to induce measurable IL-6 in the cultures that did not secrete IL-6 under basal conditions. Prostaglandin E2 did not influence basal IL-6 secretion and indomethacin did not inhibit IL-1-stimulated IL-6 release. In addition, pertussis toxin had no effect on IL-1-stimulated IL-6 release. The growth hormone (GH) secretory response to IL-1 varied, with stimulation in one GH-secreting adenoma culture, no significant effect in a second and inhibition in a third. Interleukin-1 did not significantly affect the release of prolactin, thyrotrophin, luteinizing hormone or follicle-stimulating hormone in any of the adenoma cultures. This study provides evidence that IL-1 is a stimulator of IL-6 release from cultured human pituitary adenoma cells that secrete IL-6. Stimulation of IL-6 release by IL-1 in these tumour cells is probably not mediated by prostaglandins or by a pertussis toxin-sensitive mechanism.
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PMID:Interleukin-1 stimulates the release of interleukin-6 from cultured human pituitary adenoma cells. 839 Nov 94

Tumour necrosis factor-alpha (TNF) induced a cytotoxic response in ME-180 human cervical carcinoma cells in vitro. This cytotoxic response was accompanied by a temporal series of intracellular signals that are commonly triggered by a mitogenic stimulus: increased c-fos (20-30 min) and c-myc (40-60 min) expression, increased activity of ornithine decarboxylase (3 h), increased intracellular polyamine content (7 h) and increased thymidine incorporation into DNA (14 h). A cytotoxic response independent of these mitogenic signals could not be explained by an induction of interleukin-6, which is an autocrine cytotoxic agent in some cell types; nor by a biphasic, dose-dependent response in which low concentrations of TNF are mitogenic and higher concentrations are cytotoxic. Conversely, a dependent role of these mitogenic signals was suggested by the absence of a TNF-promoted increase in thymidine incorporation into DNA in an ME-180 clone that is resistant to TNF-induced cytotoxicity. A decrease in the proliferation rate of TNF-sensitive cells induced by either alpha-difluoromethylornithine treatment (resulting in polyamine depletion) or serum starvation rendered the cells insensitive to TNF-induced cytotoxicity, further suggesting a role for mitogenic signals and cell division in TNF-mediated cytotoxicity. However, inhibiting proliferation with cycloheximide resulted in increased sensitivity to TNF, implying that mitogenesis itself was not essential for a cytotoxic response. TNF induced DNA fragmentation in sensitive cells, suggesting that cytotoxicity occurred via apoptosis.
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PMID:Tumour necrosis factor-induced cytotoxicity is accompanied by intracellular mitogenic signals in ME-180 human cervical carcinoma cells. 843 87

Tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) were detected in the intra-carpal synovial fluids collected from aborted and recently dead young calves. Five out of seven TNF-alpha positive joint fluids were bacteriologically positive and two were sterile. Only one out of 20 TNF-alpha negative joint aspirates was infected (P = 0.0014). Sixteen of the synovial fluid samples were examined for the presence of IL-6. In 12 samples IL-6 was detected, six of which were bacteriologically contaminated. Four out of the 16 samples were IL-6 negative. These findings indicated the possible association between TNF-alpha and the intra-articular inflammatory processes in young calves, which in the present study were either found in combination with or without IL-6.
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PMID:The association between tumour necrosis factor-alpha, interleukin-6 and microbiological findings in the synovial fluid of aborted and neonatal calves. 888 8

Pro-inflammatory cytokines, some of which have the capacity to modulate cartilage and bone metabolism, are important mediators of the frequently sustained and destructive inflammation that characterises rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) have been studied extensively in this regard. That these proteins are important is no longer in doubt following the demonstration that the IL-1 receptor antagonist and neutralising antibodies directed against TNF alpha are clinically effective. Recent studies suggest that interleukin-6 (IL-6) and other members of the IL-6 cytokine subfamily are also potentially important cytokines in the pathogenesis of RA. The recognition of shared molecular subunits in the receptors for these cytokines raises the possibility that components of these receptors or their derivatives, either alone or in combination, may be useful for antagonising members of the IL-6 cytokine subfamily. Effective antagonism could be therapeutically beneficial in respect to attenuating inflammation and protecting critically important chondral and skeletal tissue. In this review the rationale and possible strategies for such antagonism are discussed.
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PMID:Antagonism of the IL-6 cytokine subfamily--a potential strategy for more effective therapy in rheumatoid arthritis. 949 79

To study the role of the sympathetic nervous system in the induction of inflammatory cytokines elicited by central lipopolysaccharide, sympathetic chemical denervation was performed by intraperitoneal injection of 6-hydroxydopamine. Rats received the neurotoxin according to the following schedule: 50 mg/kg on days 1 and 2, 100 mg/kg on days 3, 4 and 7. On day 8, lipopolysaccharide (2.5 microg/6 microl/rat) was injected intracerebroventricularly and rats were killed 2 h later. 6-Hydroxydopamine reduced noradrenaline and dopamine content in the spleen by 88.7% and 88.8% respectively, without affecting striatal contents indicating that the chemical sympathectomy had been effective and selective. In sympathectomized rats, lipopolysaccharide raised interleukin-1beta and interleukin-6 serum levels more than in control rats given the vehicle. Tumour necrosis factor-alpha serum levels in sympathectomized rats were no different from those in vehicle-treated rats. Interleukin-1beta and interleukin-6 messenger RNA expression, measured by northern blot analysis, was clearly detectable in adrenals and spleen of rats given lipopolysaccharide. Sympathectomy increased lipopolysaccharide-induced interleukin-1beta and interleukin-6 messenger RNA in adrenals and spleen. Corticosterone basal levels were raised by central lipopolysaccharide and not further changed by sympathectomy. The present study shows that sympathetic nervous system denervation enhances the synthesis and production of peripheral interleukin-1beta and interleukin-6 in rats given central lipopolysaccharide and suggests a tonic inhibitory control of the sympathetic nervous system on these inflammatory cytokines.
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PMID:The sympathetic nervous system tonically inhibits peripheral interleukin-1beta and interleukin-6 induction by central lipopolysaccharide. 950 62

The peri-operative cytokine response was studied in 13 infants and young children undergoing major surgery. All children were anaesthetized with a combined general and epidural anaesthetic technique, followed by post-operative epidural analgesia with bupivacaine and fentanyl. Blood samples were taken before and after surgery, 24 h post-operatively, and finally, when the children were mobilized and had regained gastrointestinal function. Plasma samples were analysed for tumour necrosis factor-alpha, interleukin-1 alpha, interleukin-1 beta, interleukin-6, interferon-gamma, interleukin-10 and the interleukin-1 receptor antagonist. The cytokine responses were highly variable. Overall, no significant changes between pre- and post-operative plasma concentrations were found. Tumour necrosis factor-alpha and the interleukin-1 receptor antagonist were detectable in all children, and a trend towards an early increase in the interleukin-1 receptor antagonist levels at the end of surgery was seen. The other cytokines were only detectable at low concentrations among a minority of children. In conclusion, this study showed highly variable peri-operative cytokine responses in infants and young children undergoing major surgery.
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PMID:The peri-operative cytokine response in infants and young children following major surgery. 952 42

Intravenous administration of different cytokines caused important changes in the expression of ubiquitin genes in skeletal muscle. Tumour necrosis factor-alpha caused a 2.2- and 1.9-fold increase in the expression of the 2.4 and 1.2 kb transcripts, respectively. Administration of interferon-gamma also caused a 2.2- and 1.8-fold increase in the 2.4 and 1.2 kb transcripts, respectively. While administration of leukaemia inhibitory factor and interleukin-6 resulted in no changes in ubiquitin gene expression, interleukin-1 administration also caused an increase in both ubiquitin gene transcripts (2.8- and 1.9-fold for the 2.4 and 1.2 kb transcripts, respectively). The results suggest that some of the cytokine effects on the ubiquitin system gene expression could be related to the enhanced skeletal muscle proteolysis found during cancer cachexia and other pathological states.
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PMID:Different cytokines modulate ubiquitin gene expression in rat skeletal muscle. 992 64


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