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)

After stress or trauma, the serum zinc concentration decreases. This study evaluated possible mechanisms for hypozincemia with the use of a human endotoxemia model. Two doses of endotoxin [lipopolysaccharide (LPS)] were administered on consecutive mornings to 12 healthy volunteers, and each subject was also studied after saline injection. Blood was analyzed for zinc, cytokines (tumor necrosis factor-alpha and interleukin-6), albumin, albumin-zinc binding, and C-reactive protein (CRP). Serial 24-h urine collections were analyzed for zinc. Each LPS dose briefly increased plasma cytokine concentrations and decreased the serum zinc concentration. Serum albumin, the major zinc binding protein, did not decrease, but a progressive increase in CRP was found. LPS did not alter zinc binding affinity to serum albumin. Urine zinc losses were not increased. We conclude that hypozincemia in this model cannot be explained by decreased serum albumin, changes in serum albumin-zinc binding, or increased urinary zinc excretion. Because hypozincemia was transient and followed cytokine peaks, we postulate that LPS-stimulated hypozincemia is mediated, at least partly, by a cytokine-directed internal redistribution of zinc.
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PMID:Effects of endotoxin on zinc metabolism in human volunteers. 922 37

The effects of topical application of interleukin-6 (IL-6) on the short and long latency evoked unit responses of the neurones in the primary somatosensory (SI) cortex were determined quantitatively in anaesthetized rats. IL-6 (0.01, 0.1, 1.0 units) significantly suppressed (-15.13 +/- 3.4%) short latency afferent sensory responses, while it induced profound facilitation (+464.74 +/- 132.7%) of long latency responses in a dose-dependent manner. IL-6-induced afferent modulations fully recovered by 60 min after drug administration. In control experiments, saline solution containing 0.2% bovine serum albumin, used as a vehicle, did not affect afferent sensory transmission. Implications of these results are discussed with reference to the different somatosensory functions of short and long latency response components in the SI cortex.
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PMID:Differential modulation of short and long latency sensory responses in the SI cortex by IL-6. 937 15

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

We studied the prognostic significance of plasmablastic (PB) multiple myeloma (MM) in Eastern Cooperative Oncology Group Phase III trial E9486. Two reviewers independently reviewed 453 cases. They agreed on 37 PB (8.2%) cases and 416 non-PB cases, achieving an 85% concordance (P < .0001). These PB cases had significantly lower hemoglobin and serum albumin levels, higher calcium and beta 2-microglobuin levels, and higher percentage BM plasma cells (PC) by immunofluorescence. They had higher bone marrow PC labeling indices, higher serum soluble interleukin-6 receptor (sIL-6R) levels, and a higher probability of ras mutations. Three treatment regimens were used: vincristine, bis-chloro-ethyl nitrosourea (BCNU) melphalan, cyclophosphamide, and prednisone (VBMCP) alone; VBMCP with added cyclophosphamide (HiCy); or recombinant interferon alpha 2 (rIFNalpha2). Although the numbers are low, patients with PB had a significantly lower response rate versus non-PB MM when treated with VBMCP (treated, 47.1% v nontreated, 66.5% [P = .015]). Patients with nonresponding PB had a significantly higher progression rate than non-PB cases (30.6% v 11.8% [P < .0001]), especially with VBMCP alone (35.3% v 15.8% [P = .002]), and with added HiCy (37.5% v 9.8% [P < .0001]), but not with added rIFNalpha2. Event-free and overall survival of PB MM was shorter (median years, 1.1 v 2.7 and 1.9 v 3.7, respectively [P < .0001 for both]). In multivariate analysis, PB classification was also highly prognostic. There is no survival difference between the patients who were classified as PB by both reviewers versus patients classified as PB by only one reviewer. We conclude that PB MM is a discrete entity associated with more aggressive disease and shortened survival. Tumor cell ras mutations and increased sIL-6R may contribute to a higher proliferation rate and reduced survival. There were significant improvements in response and progression with the addition of HiCy and rIFNalpha2 to VBMCP, but the numbers were small and improved survival could not be shown.
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PMID:Plasmablastic morphology--an independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group. 951 51

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.
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PMID:Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients. 966 31

Induction of interleukin-6 (IL-6) secretion by whole blood cultures (WBC) was used as an in vitro assay system for pyrogen-induced inflammatory reactions. The assay system was very sensitive to Eschericia coli (E coli) endotoxin (< 10 pg/ml). The potential pyrogenic effects of human serum albumin (HSA), Fibronectin (Fn) and stabilised human serum (SHS) solutions were analyzed using this system. None of the products assayed had an effect on the sensitivity of the WBC assay. Spike recovery studies with isolated endotoxin, gram positive and gram negative bacteria showed that none of the products had an effect on the spike recovery of these pyrogenic substances. Good correlations were found between the WBC assay and the rabbit assay for pyrogens for all the production batches tested. When these samples were analysed by the limulus amoebocyte lysate (LAL) assay, the LAL test gave anomalous results for 1 out of the 22 production batches tested. This batch gave a false negative result on the LAL assay and might be indicative of the inability of the LAL assay to detect pyrogens other than endotoxin.
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PMID:The detection of pyrogens in blood products using an ex vivo whole blood culture assay. 968 26

We have used a competitive repopulation assay in baboons to develop improved methods for hematopoietic stem cell transduction and have previously shown increased gene transfer into baboon marrow repopulating cells using a gibbon ape leukemia virus (GALV)-pseudotype retroviral vector (Kiem et al, Blood 90:4638, 1997). In this study using GALV-pseudotype vectors, we examined additional variables that have been reported to increase gene transfer into hematopoietic progenitor cells in culture for their ability to increase gene transfer into baboon hematopoietic repopulating cells. Baboon marrow was harvested after in vivo administration (priming) of stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF). CD34-enriched marrow cells were divided into two equal fractions to directly compare transduction efficiencies under different gene transfer conditions. Transduction by either incubation with retroviral vectors on CH-296-coated flasks or by cocultivation on vector-producing cells was studied in five animals; in one animal, transduction on CH-296 was compared with transduction on bovine serum albumin (BSA)-coated flasks. The highest level of gene transfer was obtained after 24 hours of prestimulation followed by 48 hours of incubation on CH-296 in vector-containing medium in the presence of multiple hematopoietic growth factors (interleukin-6, stem cell factor, FLT-3 ligand, and megakaryocyte growth and development factor). Using these conditions, up to 20% of peripheral blood and marrow cells contained vector sequences for more than 20 weeks, as determined by both polymerase chain reaction and Southern blot analysis. Gene transfer rates were higher for cells transduced on CH-296 as compared with BSA or cocultivation. In one animal, we have used a vector expressing a cell surface protein (human placental alkaline phosphatase) and have detected 10% and 5% of peripheral blood cells expressing the transduced gene 2 and 4 weeks after transplantation as measured by flow cytometry. In conclusion, the conditions described here have resulted in gene transfer rates that will allow detection of transduced cells by flow cytometry to facilitate the evaluation of gene expression. The levels of gene transfer obtained with these conditions suggest the potential for therapeutic efficacy in diseases affecting the hematopoietic system.
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PMID:Improved gene transfer into baboon marrow repopulating cells using recombinant human fibronectin fragment CH-296 in combination with interleukin-6, stem cell factor, FLT-3 ligand, and megakaryocyte growth and development factor. 973 Oct 44

Eosinophils and their products play a major role in inflammatory reactions associated with asthma and allergic diseases. There is a growing body of evidence that eosinophils synthesize, store, and release bioactive cytokines and chemokines with the potential to contribute to local inflammatory changes. Fluorescein isothiocyanate (FITC) has been widely used as an immunofluorescent conjugate for antibodies specific for detection of these molecules. However, FITC is an ionic fluorochrome (negatively charged) which binds strongly to positively charged eosinophil granule proteins. We developed new methods to prevent charge-based interactions of ionic fluorochromes with granule proteins, and optimised immunofluorescent staining techniques for eosinophils. An antibody to interleukin-6 (IL-6) was used to optimise this procedure for eosinophil-derived granule proteins. We attempted to block nonspecific binding of FITC-labelled anti-IL-6 using normal human IgG, foetal calf serum (FCS), bovine serum albumin (BSA), and goat, horse, and normal human sera at concentrations ranging between 1-10%. Only human IgG (2%; 20 mg/ml) was able to reduce background fluorescence. These results were confirmed using Texas Red conjugates. We also used antibodies conjugated to a nonionic fluorochrome, BODIPY FL, to detect IL-6 in eosinophils. Unlike FITC, BODIPY FL-conjugated antibodies did not require strong blocking conditions (2% BSA). We recommend that a neutral fluorochrome (BODIPY FL) should be used for immunofluorescence studies in eosinophils. Alternatively, strong blocking conditions may be used to decrease background binding of FITC-conjugated antibodies.
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PMID:Inhibition of nonspecific binding of fluorescent-labelled antibodies to human eosinophils. 977 81

To better understand the vascular activity of hemoglobin-based (Hb-based) oxygen carriers, the endothelial permeability characteristics of Hb derivatives having various molecular masses were defined by using monolayers of bovine endothelial cells cultured on microporous membranes. The endothelial permeability of unmodified bovine Hb was almost twice that of bovine serum albumin. Intramolecularly cross-linked human Hb showed slightly but significantly reduced permeability as compared with unmodified bovine Hb. Polyethyleneglycol modification or haptoglobin binding to Hb further reduced the permeability. These properties were intensified in conditions in which the endothelial barrier function was reduced by pretreatment with either interleukin-6 (100 ng/mL, 21 hours) or lipopolysaccharide (1 microg/mL, 10 hours). In contrast, there was little permeability of liposome-encapsulated Hb, and it was almost unaffected by the pretreatments. These data provide the first information that Hb derivatives with smaller molecular masses show larger transendothelial flux. Because Hb is a potent scavenger of endothelium-derived relaxing factor (EDRF), our observations support the idea that smaller Hb-based acellular oxygen carriers are potent vasoconstrictors as a result of abluminal EDRF scavenging.
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PMID:Permeability characteristics of hemoglobin derivatives across cultured endothelial cell monolayers. 979 3

Traumatic brain injury (TBI) induces local and systemic immunologic changes, release of cytokines, and cell activation. Perpetuation of these cascades may contribute to secondary damage to the brain. Therefore, the ability of the antiinflammatory mediator transforming growth factor-beta (TGF-beta) to downregulate intrathecal immunoactivation may be of fundamental value for diminishing the incidence and extent of secondary insults. In this study, the release of TGF-beta into cerebrospinal fluid (CSF) and serum of 22 patients with severe TBI was analyzed with respect to the function of the blood-brain barrier (BBB) for 21 days. Levels of TGF-beta in CSF increased to their maximum on the first day (median, 1.26 ng/mL), thereafter decreasing gradually over time. Median TGF-beta values in serum always remained within the reference interval (6.5 to 71.5 ng/mL). Daily assessment of the CSF-serum albumin quotient (QA) and of the CSF-serum TGF-beta quotient (QTGF-beta) showed a strong correlation between maximal QTGF-beta and QA, indicating a passage of this cytokine from the periphery to the intrathecal compartment across the BBB. However, calculation of the TGF-beta index (QTGF-beta/Q(A)) suggested a cerebral production of TGF-beta in 9 of 22 patients. Levels of TGF-beta could not be correlated with extent of initial injury by computed tomography (CT), CD4/CD8 ratios, acute lung injury, or clinical outcome as rated by the Glasgow Outcome Scale (GOS). Although increased levels of TGF-beta in CSF seem to parallel BBB function, a partial intrathecal production is suggested, possibly modulated by elevation of interleukin-6 (IL-6). Thus, TGF-beta may function as a factor in the complex cytokine network following TBI, acting as an antiinflammatory and neuroprotective mediator.
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PMID:TGF-beta is elevated in the CSF of patients with severe traumatic brain injuries and parallels blood-brain barrier function. 1044 73


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