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 tested the hypothesis that voluntary running and moderate food restriction alter the acute phase response (APR), one index of nonspecific immune function. Hamsters were kept sedentary or permitted to run and were fed ad libitum or had food restricted for 20 days and were then injected intraperitoneally with saline or lipopolysaccharide (LPS). Fever and circulating interleukin-6, serum amyloid A (SAA), serum iron, and cortisol were measured by biotelemetry, B-9 cell growth assay, indirect enzyme-linked immunosorbent assay, colorimetric analysis, and radioimmunoassay, respectively. The febrile temperature; hypoferremia; and elevation of circulating interleukin-6, SAA, and cortisol after LPS injection were not altered by exercise. Because baseline temperatures were elevated in the exercised hamsters, the change in temperature in response to LPS was less than it was in the sedentary hamsters. Food restriction significantly decreased SAA and elevated cortisol after LPS injection and depressed the absolute temperature to which the core temperature rose in response to LPS in one trial but not in another. Because food restriction depressed baseline temperatures, it also affected the change in temperature after LPS injection. The hypoferremic response to LPS was inhibited in hamsters that were both food restricted and permitted to run. We conclude that exercise does not enhance the APR to a low dose of LPS, whereas food restriction and the combination of exercise and food restriction depress some portions of the APR in hamsters.
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PMID:Effect of voluntary exercise and food restriction in response to lipopolysaccharide in hamsters. 775 14

To define the toxicity profile of recombinant human interleukin-6 (rhIL-6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6-related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL-6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.
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PMID:Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study. 806 39

To understand the mechanisms by which large increases in serum amyloid A (SAA) occur during the acute phase response, human hepatoma cells were transfected with SAA2 gene reporter plasmids and stimulated with combinations of cytokines. Although interleukin-1 (IL-1) and interleukin-6 (IL-6) stimulated transcription from this promoter individually, addition of both mediators produced a response between two and nine times greater than the expected additive response. This synergistic activation was dependent on the integrity of at least two cis-acting sequences in the SAA2 enhancer. The SAA2 NF-kappa B site was required functionally for the response to both IL-1 and IL-6 alone as well as for synergistic activation; however, IL-6 did not directly induce binding of nuclear proteins to the NF-kappa B sequence. A NF-IL6 site was required for full induction by IL-1 and IL-6, and also mediated strong transactivation by recombinant NF-IL6. Furthermore, transfected NF-IL6 synergized strongly with co-transfected NF-kappa B, particularly with RelA (p65). However synergy between IL-1 and IL-6 was only partly reduced by mutation of the NF-IL6 site, indicating further levels of interaction in addition to the NF-kappa B/NF-IL6 cooperativity.
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PMID:The role of NF-kappa B and NF-IL6 transactivating factors in the synergistic activation of human serum amyloid A gene expression by interleukin-1 and interleukin-6. 824 97

Ciliary neurotrophic factor (CNTF) and interleukin-6 (IL-6) potentiate the elevation of serum corticosterone induced by suboptimal doses of interleukin-1 (IL-1). CNTF also potentiates IL-1-induced serum IL-6. Here, we report that four other cytokines (leukemia inhibitory factor [LIF], oncostatin M [OSM], interleukin-11 and cardiotrophin-1) also potentiated the elevation of serum corticosterone and IL-6 levels induced by IL-1. Furthermore, all the six cytokines studied induced the acute-phase protein serum amyloid A when administered alone. Because these cytokines differ both in structure and in function, but share gp130 as a subunit of their receptors, these results indicate that signaling through gp130 mediates potentiation of IL-1 activities. The potentiation of IL-1-induced serum corticosterone levels is not a consequence of the increased serum IL-6 observed after IL-1 administration. In fact, in IL-6 deficient mice, IL-1 increased serum corticosterone to a level comparable to that observed in wild-type mice. Thus, either endogenous IL-6 does not mediate IL-1-induced corticosterone increase, or its role may be fulfilled by other cytokines. To the extent that gp130-dependent cytokines may serve this role, they may be important feedback regulators of inflammation through the activation of the hypothalamus-pituitary-adrenal axis and the potentiation of acute-phase protein synthesis.
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PMID:Six different cytokines that share GP130 as a receptor subunit, induce serum amyloid A and potentiate the induction of interleukin-6 and the activation of the hypothalamus-pituitary-adrenal axis by interleukin-1. 863 32

We evaluated in peritonitis-free patients undergoing continuous ambulatory peritoneal dialysis (CAPD) the release of both interleukin-6 (IL-6) and beta-2-microglobulin (beta 2m) by cultured peripheral blood mononuclear cells (PBMC), as well as the levels of serum amyloid A (SAA), that is, the main hepatic acute phase protein during inflammation. The same measurements were obtained in hemodialysis (HD) patients, uremic non-dialyzed patients (ESRD) and healthy controls (CON). In CAPD, IL-6 production from PBMC was markedly increased in comparison to the control value (600.7 +/- 104.3 vs. 14.2 +/- 3.6 pg/3 x 10(6) PBMC/24 hr, P < 0.005). Similarly, a striking enhancement of the PBMC release of beta 2m was detected in CAPD with respect to CON (10.1 +/- 2.6 vs. 0.063 +/- 0.013 micrograms/3 x 10(6) PBMC/24 hr, P < 0.001). Also, the SAA levels were significantly greater in CAPD patients (21.3 +/- 8.7 micrograms/dl) than in controls (3.14 +/- 0.17 micrograms/dl, P < 0.05). Analogous increases of both IL-6 and beta 2m cell releases, as well as of SAA levels, were observed in HD patients. No difference concerning the three parameters was detected between CON and ESRD. In conclusion, CAPD induces per se PBMC activation with an enhanced release of both IL-6 and beta 2m; this is associated to higher levels of SAA. These systemic inflammatory effects are comparable to those observed in HD patients indicating that CAPD is similar to HD in terms of biocompatibility of the treatment.
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PMID:Inflammatory effects of peritoneal dialysis: evidence of systemic monocyte activation. 882 37

Rheumatoid arthritis (RA) has no firm etiologic basis. It progresses as an autoimmune disease and evolves into a chronic inflammatory joint disease complicated by recurrent episodes of systemic acute-phase reactions, which sometimes result in amyloidosis. Cytokines play a pivotol role in inflammation and the immune response. Proinflammatory cytokines such as interleukin-1, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 are present at high levels in arthritic joints, and their blood concentration correlates with the severity of the RA. Some of the activities of the proinflammatory cytokines, such as stimulation of leukocyte infiltration and release of their proteolytic enzymes, may be mediated by acute phase proteins (APPs), such as C-reactive protein and serum amyloid A, and by chemokines such as interleukin-8. Cytokines, chemokines, and APPs reciprocally regulate each others' expression and activities, constituting a communication network between fibroblasts, macrophages, lymphocytes, and hepatocytes. Activation of the network results in inflammation and the progressive destruction of joints and systemic symptoms characteristic of RA.
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PMID:Role of cytokines, acute-phase proteins, and chemokines in the progression of rheumatoid arthritis. 891 97

The effect of a prolonged low dose infusion of bacterial lipopolysaccharide (LPS) on acute phase-like reactions was examined in heifers. LPS (2 micrograms kg-1 dissolved in 100 ml water), or saline was infused (at 1 ml min-1) intravenously for 100 minutes and blood samples were taken at various times before, during and after the infusion. The serum concentrations of tumour necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and serum amyloid A (SAA) and the rectal temperature increased in response to the LPS infusion. Serum TNF alpha increased before the increases in IL-1 beta and IL-6 and remained high from 20 minutes after the onset of the infusion until the end of the sampling period (six hours). The LPS-induced increases in serum IL-1 beta and IL-6 were biphasic. Plasma cortisol and lactate concentrations also increased, and plasma glucose and beta-hydroxybutyrate concentrations decreased in response to the LPS infusion. The similarity of these reactions to changes observed in response to bacterial infections shows that the prolonged infusion of low doses of LPS is a good model for studying the acute phase response to Gram-negative bacterial infection in heifers.
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PMID:Characterisation of the acute phase response of heifers to a prolonged low dose infusion of lipopolysaccharide. 893 57

The effects of methyl palmitate (MP), a known inhibitor of Kupffer cells, were studied in a model of polymicrobial sepsis induced in CD-1 mice by cecal ligation and puncture (CLP). The inhibition of Kupffer cells by pretreatment with MP was shown by the reduced phagocytosis, the production of tumor necrosis factor (TNF) and interleukin-6 (IL-6) after lipopolysaccharide (LPS) challenge. The reduced activation of Kupffer cells resulted in lower levels of inflammatory products after CLP. TNF and IL-6 were significantly reduced in serum 2 h and 24 h respectively after CLP, interleukin-1 beta (IL-1 beta) was reduced in liver 4 h after CLP, nitric oxide (NO) and serum amyloid A (SAA) were significantly reduced 8 and 24 h respectively after CLP. Liver toxicity was significantly reduced in MP-treated mice and survival was significantly prolonged at all intervals, reaching 45% after six to ten days compared with 3% in control mice. These findings suggest that Kupffer cells play an important role in liver damage and survival in sepsis.
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PMID:Effects of methyl palmitate on cytokine release, liver injury and survival in mice with sepsis. 901 Jun 79

Impairment of splanchnic and peripheral tissue perfusion during cardiopulmonary bypass (CPB) may be responsible for endotoxin-mediated systemic inflammation and acute phase responses. We examined the effects of dopexamine on hemodynamic parameters, creatinine clearance, systemic and splanchnic oxygenation, gastric mucosal pH (pHi), and mixed and hepatic venous plasma levels of endotoxin, interleukin-6 (IL-6), serum amyloid A (SAA), and C-reactive protein (CRP) in 44 patients scheduled for coronary artery bypass grafting. Patients were randomized to receive continuous infusions of 0.5, 1.0, or 2 micrograms.kg-1.min-1 dopexamine (n = 10 per group) or placebo (n = 14) prior to surgery, intraoperatively, and postoperatively. Dopexamine infusion increased systemic oxygen delivery (P < or = 0.01). Hepatic venous oxygen saturation did not change, and pHi decreased during and after CPB in all patients (P < or = 0.01). Postoperative increases in IL-6 were smallest in patients who received 2.0 micrograms.kg-1.min-1 dopexamine (P < or = 0.02). SAA and CRP increases during the postoperative period were less pronounced with dopexamine throughout the study. Creatinine clearance was elevated in all dopexamine groups (P < or = 0.025). This elevation was higher with lower dopexamine doses (P < or = 0.025). We conclude that dopexamine improves creatinine clearance and reduces systemic inflammation without affecting splanchnic oxygenation.
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PMID:Effects of dopexamine on creatinine clearance, systemic inflammation, and splanchnic oxygenation in patients undergoing coronary artery bypass grafting. 914 14

Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertriglyceridaemia, low serum HDL-cholesterol concentrations, hypertension, obesity and accelerated atherosclerosis (metabolic syndrome X). Since a similar dyslipidaemia occurs with the acute-phase response, we investigated whether elevated acute-phase/stress reactants (the innate immune system's response to environmental stress) and their major cytokine mediator (interleukin-6, IL-6) are associated with NIDDM and syndrome X, and may thus provide a unifying pathophysiological mechanism for these conditions. Two groups of Caucasian subjects with NIDDM were studied. Those with any 4 or 5 features of syndrome X (n = 19) were compared with a group with 0 or 1 feature of syndrome X (n = 25) but similar age, sex distribution, diabetes duration, glycaemic control and diabetes treatment. Healthy non-diabetic subjects of comparable age and sex acted as controls. Overnight urinary albumin excretion rate, a risk factor for cardiovascular disease, was also assayed in subjects to assess its relationship to the acute-phase response. Serum sialic acid was confirmed as a marker of the acute-phase response since serum concentrations were significantly related to established acute-phase proteins such as alpha-1 acid glycoprotein (r = 0.82, p < 0.0001). There was a significant graded increase of serum sialic acid, alpha-1 acid glycoprotein, IL-6 and urinary albumin excretion rate amongst the three groups, with the lowest levels in non-diabetic subjects, intermediate levels in NIDDM patients without syndrome X and highest levels in NIDDM patients with syndrome X. C-reactive protein and cortisol levels were also higher in syndrome X-positive compared to X-negative patients and serum amyloid A was higher in both diabetic groups than in the control group. We conclude that NIDDM is associated with an elevated acute-phase response, particularly in those with features of syndrome X. Abnormalities of the innate immune system may be a contributor to the hypertriglyceridaemia, low HDL cholesterol, hypertension, glucose intolerance, insulin resistance and accelerated atherosclerosis of NIDDM. Microalbuminuria may be a component of the acute-phase response.
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PMID:NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. 2212 8


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