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 summary, we established that a significant production of the monokines interleukin-6, tumor necrosis factor apha, and interleukin-1 occurred during orthotopic liver transplantation whereas the lymphokines interferon gamma and interleukin-2 were not detected. Levels of interleukin-6 reached their maximum values before and especially at the end of the anhepatic phase. They remained high after the anhepatic phase, i. e. after reperfusion of the new livers. Tumor necrosis factor alpha and interleukin-1 reached their maximum values after the anhepatic phase. Not only were interleukin-6, tumor necrosis factor alpha, and interleukin-1 present in the serum but they could also be detected in the bile produced by these new livers. Mechanisms of monokine production during orthotopic liver transplantation is multifactorial in origin and further studies will have to evaluate the relative contribution of the various factors involved. The possibility of an association between peroperative monokines and transplant outcome and their potential clinical implication will have to be elucidated.
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PMID:Intraoperative cytokines production during orthotopic liver transplantation. 1462 95

Periodontopathic anaerobes such as Porphyromonas gingivalis are frequently found in aspiration pneumonia and lung abscesses. However, defense mechanisms and responses to these bacterial infections in the lung in vivo remain poorly understood. The coexistence of P. gingivalis with Treponema denticola has been found at higher levels and proportions in periodontally diseased sites. We hypothesized that mixed infections with P. gingivalis and T. denticola can cause severe respiratory disease. In the present study, inflammatory responses to mono- and mixed inoculations with P. gingivalis and T. denticola in the bronchoalveolar lavage (BAL) fluid were investigated. Acute pneumonia and lung abscesses in mice with the mixed infection resulted in a 40% mortality rate within 72 h, compared with only 10% mortality for the respective monoinfections. Pulmonary clearance of P. gingivalis was delayed in the mice with mixed infections with P. gingivalis and T. denticola. Tumor necrosis factor alpha (TNFalpha) interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels from BAL fluid of mice with mixed infections at 24 h after inoculation were significantly higher than those after P. gingivalis monoinfection (TNFalpha: P < 0.05, Il-1beta: P < 0.001, IL-6: P < 0.05). The chemokine KC level from BAL fluid of mice at 48 h (P < 0.05) and 72 h after mixed infection was also significantly increased when compared with that after P. gingivalis monoinfection (P < 0.001). The present study demonstrates that a mixed infection of P. gingivalis with T. denticola in mouse causes a marked bronchopneumonia and lung abscess in the mouse model.
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PMID:Mixed infections with Porphyromonas gingivalis and Treponema denticola cause excessive inflammatory responses in a mouse pneumonia model compared with monoinfections. 1467 Apr 48

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase secreted by cultured human osteoblasts that has been implicated in the regulation of local insulin-like growth factor (IGF) bioavailability during bone growth and remodeling. However, very little is known about the regulation of PAPP-A expression in bone. In this study, we determined the effect of systemic and local osteoregulatory factors on PAPP-A mRNA and protein expression in normal human osteoblasts (hOB cells). Treatment of hOB cells with particular peptide growth factors (basic fibroblast growth factor, epidermal growth factor), steroid hormones (dexamethasone, 1,25-dihydroxyvitamin D(3)), and cytokines [interleukin-6 (IL-6), IL-13, oncostatin M] with known involvement in bone cell physiology had no significant effect on PAPP-A expression. Agents that increase intracellular cyclic AMP (forskolin, prostaglandin E(2)) increased PAPP-A mRNA and protein expression approximately 3-fold. Tumor necrosis factor alpha (TNFalpha), IL-1beta, and IL-4 also increased PAPP-A expression 3- to 4-fold. Transforming growth factor beta (TGFbeta) was previously shown to stimulate PAPP-A expression in hOB cells. The effects of TGFbeta, TNFalpha, and IL-1beta were additive, whereas the effects of TGFbeta and IL-4 were synergistic. In summary, TNFalpha, IL-1beta, and IL-4 were identified as potent stimulators of PAPP-A expression in primary cultures of human osteoblasts. These findings suggest a mechanism whereby cytokines present in bone and bone marrow could augment IGF bioavailability during skeletal growth and remodeling.
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PMID:Regulation of pregnancy-associated plasma protein-A expression in cultured human osteoblasts. 1496 8

Electrical resistance across human umbilical vein endothelial cells (HUVECs) was measured using an electrical cell sensor system. The transendothelial electrical resistance (TEER) value was used to estimate the permeability through endothelial cells in vitro. Decrease in the TEER value was associated with increase in the passage of albumin through endothelial cells in the albumin permeability assay. The effects of cytokines and dengue virus infection on the permeability of HUVECs were examined by measuring the TEER value. Tumor necrosis factor alpha (TNF-alpha) at 1 and 0.1 microg/ml decreased the TEER value, but TNF-alpha at lower dose did not. Interferon-gamma (IFN-gamma) at 1 microg/ml also decreased the TEER value. In contrast, interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) or interferon-beta (IFN-beta) did not decrease the TEER value. The decrease in the TEER value was associated with the morphological changes of HUVECs. Dengue virus infection at a multiplicities of infection (m.o.i.) of 5 pfu/cell decreased the TEER value. Infection at an m.o.i. of 0.5 pfu/cell did not decrease the TEER value; however, addition of 0.01 microg/ml of TNF-alpha to these infected endothelial cells decreased the TEER value. The results suggest that TNF-alpha and dengue virus infection decrease synergistically the TEER value of endothelial cells. The TEER method is easy, reliable and can be applicable to further analysis of the increase in the permeability of endothelial cells in vitro induced by inflammatory cytokines and dengue virus infection.
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PMID:In vitro assessment of human endothelial cell permeability: effects of inflammatory cytokines and dengue virus infection. 1538 54

Cardiac surgery with cardiopulmonary bypass (CPB) elicits an inflammatory response and has a multitude of biological consequences, ranging from subclinical organ dysfunction to severe multiorgan failure. Pediatric patients are more prone to have a reaction that can jeopardize their outcome. Cytokines are supposed to be important mediators in this response: limiting their circulating levels is, therefore, appealing. We investigated the pattern of cytokine release during pediatric operation for congenital heart anomalies in 20 patients, and the effect of hemofiltration. Tumor necrosis factor alpha (TNF-alpha) was elevated after anesthesia induction and showed significant decrease during CPB. Hemofiltration reduced its concentration, but the effect disappeared on the following day. Interleukin-1 (IL-1) increased slowly at the end of CPB and hemofiltration had no effect. Interleukin-6 (IL-6) showed a tendency toward augmentation during rewarming and hemofiltration did not significantly affect the course. Soluble interleukin-6 receptor (sIL-6r) had a pattern similar to TNF-alpha, but hemofiltration had no effect. On the other hand, interleukin-8 (IL-8) behaved like IL-6. Our findings suggest that baseline clinical status, anesthetic drugs, and maneuvers before incision may elicit a cytokine response, whereas rewarming is a critical phase of CPB. Hemofiltration is effective in removal of TNF-alpha, but its role is debatable for the control of IL-1, IL-6, sIL-6r and IL-8 levels.
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PMID:Inflammatory cytokines in pediatric cardiac surgery and variable effect of the hemofiltration process. 1623 22

In vitro mammary epithelial cell models typically fail to form a consistently tight barrier that can effectively separate blood from milk. Our hypothesis was that mammary epithelial barrier function would be affected by changes in luminal ion concentration and inflammatory cytokines. Bovine mammary epithelial (BME-UV cell line) cells were grown to confluence on permeable supports with a standard basolateral medium and either high-electrolyte (H-elec) or low-electrolyte (L-elec) apical medium for 14 days. Apical media were changed to/from H-elec medium at predetermined times prior to assay. Transepithelial electrical resistance (R(te)) was highest in monolayers continuously exposed to apical L-elec. A time-dependent decline in R(te) began within 24 h of H-elec medium exposure. Change from H-elec medium to L-elec medium time-dependently increased R(te). Permeation by FITC-conjugated dextran was elevated across monolayers exposed to H-elec, suggesting compromise of a paracellular pathway. Significant alteration in occludin distribution was evident, concomitant with the changes in R(te), although total occludin was unchanged. Neither substitution of Na(+) with N-methyl-d-glucosamine (NMDG(+)) nor pharmacological inhibition of transcellular Na(+) transport pathways abrogated the effects of apical H-elec medium on R(te). Tumor necrosis factor alpha, but not interleukin-1beta nor interleukin-6, in the apical compartment caused a significant decrease in R(te) within 8 h. These results indicate that mammary epithelium is a dynamic barrier whose cell-cell contacts are acutely modulated by cytokines and luminal electrolyte environment. Results not only demonstrate that BME-UV cells are a model system representative of mammary epithelium but also provide critical information that can be applied to other mammary model systems to improve their physiological relevance.
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PMID:Apical electrolyte concentration modulates barrier function and tight junction protein localization in bovine mammary epithelium. 1688 91

Bacterial DNA (bactDNA) is present in blood and ascitic fluid (AF) in a third of patients with cirrhosis and ascites, but whether this phenomenon represents episodes of bacterial translocation (BT), strictly considered when culture of mesenteric lymph nodes (MLNs) are positive, remains unknown. This study assessed the relationship between bactDNA detection in biological fluids and MLNs and went on to investigate the local and systemic inflammatory status according to its presence. Cirrhosis was induced in rats by ingestion of CCL4. A subgroup of five animals with cirrhosis received norfloxacin (5 mg/kg/day) for 7 days. MLNs and ascitic and pleural fluids were collected at laparotomy and cultured; samples were collected for identification of bactDNA and measurement of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO). BactDNA was detected in MLNs in 12 of 19 animals (63.1%), corresponding in seven cases to culture-positive MLNs, and in five to culture-negative MLNs. BactDNA was detected in biological fluids in 11 of 19 animals (57.9%), and in all cases the same bacteria spp. detected in samples was present in MLNs. BactDNA was not detected in any biological sample from animals receiving norfloxacin. Tumor necrosis factor alpha (TNF-alpha), IL-6, and NO were similar in culture-positive and culture-negative/bactDNA-positive samples, and significantly higher than those observed in animals with culture-negative/bactDNA-negative MLNs, animals with cirrhosis that were receiving norfloxacin, and controls. In conclusion, the presence of bactDNA in biological fluids in rats with cirrhosis constitutes a marker of BT, and it is associated with a marked inflammatory response, independent of the result of the culture.
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PMID:The detection of bacterial DNA in blood of rats with CCl4-induced cirrhosis with ascites represents episodes of bacterial translocation. 1694 89

Systemic low-grade inflammation is recognized in an increasing number of chronic diseases. With the aim of establishing an experimental human in vivo model of systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of Escherichia coli endotoxin (0.3 ng/kg of body weight) either as a bolus injection or as a 4-h continuous intravenous infusion, as well as after saline administration, in 10 healthy male subjects on three separate study days. Only bolus endotoxin caused an increase in heart rate, whereas a slight increase in rectal temperature was observed in both endotoxin groups. Tumor necrosis factor alpha (TNF-alpha), interleukin-6, and neutrophil responses were earlier and more pronounced in the bolus trial compared with the infusion trial results, whereas lymphocytes increased after endotoxin bolus injection as well as infusion without any difference between groups. Finally, endotoxin activated the hypothalamo-pituitary-adrenal axis slightly earlier in the bolus compared to the infusion trial. The continuous endotoxin infusion model may be more representative of human low-grade inflammation than the bolus injection model due to a less dynamic and more sustained increase in circulating levels of inflammatory mediators over time. In conclusion, low-dose endotoxin infusion elicits an inflammatory response, as assessed by a rise in TNF-alpha, and the responses are significantly different according to whether low-dose endotoxin is applied as a bolus injection or as a continuous infusion.
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PMID:Human models of low-grade inflammation: bolus versus continuous infusion of endotoxin. 1726 90

Tumor necrosis factor alpha (TNFalpha) is a pleiotropic cytokine with several CNS physiological and pathophysiological actions including sleep, memory, thermal and appetite regulation. Short interfering RNAs (siRNA) targeting TNFalpha were incubated with cortical cell cultures and microinjected into the primary somatosensory cortex (SSctx) of rats. The TNFalpha siRNA treatment specifically reduced TNFalpha mRNA by 45% in vitro without affecting interleukin-6 or gluR1-4 mRNA levels. In vivo the TNFalpha siRNAalpha reduced TNFalpha mRNA, interleukin-6 mRNA and gluR1 mRNA levels compared to treatment with a scrambled control siRNA. After in vivo microinjection, the density of TNFalpha-immunoreactive cells in layer V of the SSctx was also reduced. Electroencephalogram (EEG) delta wave power was decreased on days 2 and 3 on the side of the brain that received the TNFalpha siRNA microinjection relative to the side receiving the control siRNA. These findings support the hypothesis that TNFalpha siRNA attenuates TNFalpha mRNA and TNFalpha protein in the rat cortex and that those reductions reduce cortical EEG delta power. Results also are consistent with the notion that TNFalpha is involved in CNS physiology including sleep regulation.
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PMID:TNFalpha siRNA reduces brain TNF and EEG delta wave activity in rats. 1753 Dec 9

Negative regulation of cytokine signaling is critical for the generation of the appropriate cellular outcome in response to signals, and can be modulated by other concomitant extracellular stimuli ("crosstalk"). Using both genetic and pharmacological manipulations we have investigated the mechanisms by which the pro-inflammatory stimuli, lipopolysaccharide (LPS) and Tumor necrosis factor alpha (TNFalpha), negatively regulate interleukin-6 (IL-6) signaling in primary mouse macrophages. Analysis of suppressor of cytokine signalling 3 (SOCS3)-deficient macrophages reveal that SOCS3 is necessary but surprisingly, not sufficient for the complete crosstalk inhibition of IL-6 signaling induced by LPS and TNFalpha. Analysis of macrophages from gp130 (Y757F) mutant mice suggest that SH2 domain-containing tyrosine phosphatase (SHP2) activity does not explain the residual inhibitory effect of these pro-inflammatory stimuli. In addition, p38 mitogen-activated protein kinase (p38) activation also negatively regulates IL-6 signaling independent of its parallel and necessary action to induce SOCS3 expression. Finally, we have identified an additional, novel mechanism of crosstalk inhibition: a reduction in total cellular levels of gp130 following stimulation with LPS and TNFalpha.
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PMID:Mechanism of crosstalk inhibition of IL-6 signaling in response to LPS and TNFalpha. 1823 10


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