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)

Acute muscular exercise induces an increased neutrophil count concomitant with recruitment of natural killer (NK), B and T cells to the blood as reflected by an elevation in the total lymphocyte count. Meanwhile, following intense exercise of long duration the lymphocyte count declines, non-MHC-restricted cytotoxicity is suppressed, but the neutrophil concentration increases. In relation to eccentric exercise involving muscle damage, the plasma concentrations of interleukin-1, interleukin-6 and the tumor necrosis factor are elevated. In this review we will propose a model based on the possible roles that stress hormones play a mediating the exercise- related immunological changes: adrenaline and to a lesser degree noradrenaline are responsible for the immediate effects of exercise on lymphocyte subpopulations and cytotoxic activities. The increase in catecholamines and growth hormone mediate the acute effects of exercise on neutrophils, whereas cortisol may be responsible for maintaining lymphopenia and neutrocytosis after exercise of long duration. Lastly, the role of beta-endorphin is less clear, but the cytokine response is closely related to muscle damage and stress hormones do not seem to be directly involved in the elevated cytokine level. Other possible mechanisms of exercise-induced immunomodulation may include the so-called glutamine hypothesis, which is based on the fact that skeletal muscle is an important source of glutamine production and that lymphocytes are dependent on glutamine for optimal growth. Furthermore, physiological changes during exercise, e.g. increased body temperature and decreased oxygen saturation may also in theory contribute to the exercise-induced immunological changes.
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PMID:Exercise-induced immunomodulation--possible roles of neuroendocrine and metabolic factors. 912 58

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

Endotoxin causes acute lung injury resembling acute respiratory distress syndrome. Elastase, as well as reactive oxygen species released from activated neutrophils, are thought to play pivotal roles in the pathogenesis of this lung injury. This study investigated whether ONO-5046, a specific elastase inhibitor, can attenuate acute lung injury induced by endotoxin in rabbits. Thirty-two male anesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 for each group): infusion of saline without ONO-5046 treatment (Group S-S), infusion of saline with ONO-5046 (Group S-O), infusion of Escherichia coli endotoxin (100 micrograms/kg over 60 min) without ONO-5046 (Group E-S), and infusion of endotoxin with ONO-5046 (Group E-O). Fifteen minutes before the infusion of endotoxin (Groups E-O and E-S) or saline (Groups S-S and S-O), the animals received a bolus injection of ONO-5046 (10 mg/kg) followed by continuous infusion (10 mg.kg-1.h-1: Groups S-O and E-O) or saline (Groups S-S and E-S). The lungs of the rabbits were ventilated with 40% oxygen. Hemodynamics, peripheral leukocyte and platelet counts, and PaO2 were recorded during the ventilation period (6 h). Lung mechanics, cell fraction of the bronchoalveolar lavage fluid (BALF), activated complement, cytokines, and arachidonic acid metabolite concentrations in the BALF were measured at 6 h. The wet- to dry (W/D)-weight ratio of the lung and albumin concentrations in BALF were analyzed as indices of pulmonary edema. Endotoxin decreased lung compliance and PaO2, and increased the W/D weight ratio, neutrophil counts, and albumin concentration in the BALF. Concentrations of activated complement C5a, interleukin-6, interleukin-8, and thromboxane B2 in the BALF were increased by the infusion of endotoxin. ONO-5046 treatment attenuated these changes. Endotoxin caused extensive morphologic lung damage, which was lessened by ONO-5046. In conclusion, intravenous ONO-5046 pretreatment attenuated endotoxin-induced lung injury in rabbits. This beneficial effect of ONO-5046 may be due, in part, to a reduction in the levels of mediators that activate neutrophils, in addition to the direct inhibitory effect on elastase.
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PMID:ONO-5046, an elastase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits. 914 38

Although paracetamol is routinely used to control fever in African children with Plasmodium falciparum, the usefulness of this treatment has not been established. In a randomized clinical trial, 50 children 2-7 years of age from Lambarene, Gabon, with P. falciparum malaria were treated with intravenous quinine and received either mechanical antipyresis alone (electric fanning, tepid sponging, and cool blankets) or in combination with paracetamol. The mean fever clearance time was 32 hours for children treated with paracetamol and 43 hours for those who received antipyresis alone--a nonsignificant difference. Parasite clearance time was significantly prolonged (by an average of 16 hours) in children who received paracetamol. Although plasma concentrations of tumor necrosis factor and interleukin-6 were similar in both groups, induced concentrations of tumor necrosis factor and the production of oxygen radicals were significantly lower in paracetamol-treated children. Overall, these findings indicate that paracetamol confers no benefits over mechanical antipyresis alone and actually prolongs parasite clearance time. Further studies are required, however, before recommendations for ancillary treatment can be changed.
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PMID:Effect of paracetamol on parasite clearance time in Plasmodium falciparum malaria. 941 85

Cytokines are proteins with pleiotropic biological effects, but the pathophysiologic role of cytokine inhibitors in advanced cardiac disease remains unclear. We assessed the levels of tumor necrosis factor (TNF)-alpha and its soluble receptors I (sTNF-RI) and II (sTNF-RII), soluble interleukin-1 receptor antagonist (sIL-1 Ra), and interleukin-6 soluble receptor (IL-6 sR) in sera from 11 patients with severe chronic congestive heart failure (mean left ventricular ejection fraction 19 +/- 6%; mean symptom-limited oxygen consumption 13 +/- 4 ml/min per kg) and 11 healthy volunteers. The serum concentrations of TNF, sTNF-RI, and sIL-1 Ra, but not of sTNF-RII and IL-6 sR, were significantly increased in heart failure patients. Importantly, their symptom-limited oxygen consumption was strongly associated with both sTNF-RI (R = -0.68, p = 0.04) and sIL-1 Ra (R = -0.77, p = 0.01). These results suggest that cytokine inhibitors from different receptor families may be involved in functional disability, a characteristic feature in patients with severe congestive heart failure. Understanding the response of cytokine inhibitors to heart failure might have therapeutic value as interventions against cytokines become available.
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PMID:Cytokine inhibitors in patients with heart failure and impaired functional capacity. 929 4

Deleterious environmental stimuli cause the airway epithelium to respond with increased secretions of mucus, reaction of oxygen/nitrogen species, changes in ciliary beating, and the influx of inflammatory cells. The epithelium is a target for factors released by infiltrating inflammatory cells, and has recently been shown to serve as an effector of such inflammation. Molecular mechanisms regulating production of secondary inflammatory mediators (cytokines, lipid mediators, and reactive oxygen/nitrogen species) have yet to be fully described. This report reviews the production of secondary mediators by epithelial cells and by airway epithelium. Lipid mediators are enzymatically produced by the airway epithelium in response to primary mediators. Molecular mechanisms regulating the production of cyclo-oxygenase, lipoxygenase and prostaglandin synthase are discussed, along with the potential of lipid mediators to produce inflammation. The molecular regulation of nitric oxide production is also described in the context of its role as a signalling molecule in pathways regulating secretion of mucus, ciliary motion, and intercellular adhesion molecule-1 (ICAM-1) expression. The production of cytokines by the airway epithelium is shown to play a role in causing inflammation associated with respiratory diseases. Particular attention is paid to molecular mechanisms governing the expression of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-8 (IL-8).
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PMID:Airway epithelium as an effector of inflammation: molecular regulation of secondary mediators. 931 17

Hemodynamics and oxygen variables, plasma cytokines, and histological features of a liver tissue sample obtained by transvenous biopsy were evaluated during 65 episodes of acute rejection. The hepatic venous pressure gradient was significantly higher in patients with acute rejection than in those without (5.1+/-0.3 vs. 3.1+/-0.2 mmHg, P<0.01). The increase in pressure gradient was related to the severity of rejection lesions. Hepatic blood flow was significantly lower in patients with than in those without acute graft rejection (1.28+/-0.11 vs. 1.75+/-0.13 L/min, P<0.05). Plasma interleukin-6 levels were significantly increased in patients with acute rejection and positively correlated with pressure gradient values. In patients with acute rejection, a significant decrease in hepatic venous oxygen content (-16%) was associated with a significant increase in hepatic oxygen consumption (+24%), whereas hepatic oxygen transport did not change significantly. In treated patients with a favorable response, the pressure gradient decreased significantly by 46%, but it remained elevated in patients who later developed chronic graft rejection. In conclusion, this study confirms that acute graft rejection may induce an increase in portal pressure, which is related to the severity of rejection lesions. It also shows that acute rejection decreases hepatic blood flow and increases hepatic oxygen consumption. In addition, it suggests that the hepatic venous pressure gradient might be useful to determine the outcome of rejection.
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PMID:Studies of portal hemodynamics and hepatic oxygen consumption during acute liver allograft rejection. 935 38

The effects of acellular hemoglobin-based oxygen carriers in preclinical models of sepsis and endotoxemia have been inconclusive with regard to outcomes reported for survival. In the present study, mice were infused with 1 gm/kg of recombinant human hemoglobin, rHb1.1, and the effects on mortality and systemic tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels were determined by using both lethal and sublethal bolus endotoxin challenge. Pretreatment of mice with rHb1.1 and challenge with 20 mg/kg of lipopolysaccharide (LPS) at an LD100 resulted in a 100% mortality rate by 20 hours, whereas the same mortality rate with the vehicle or 5% albumin groups occurred at 50 hours. Mice challenged with lower LPS concentrations of 10 and 2.5 mg/kg, corresponding to LD15 and LD0, respectively, had 100% and 17% mortality rates in the rHb group and 17% and 0% mortality rates in the vehicle-treated animals. These doses of LPS resulted in maximal increases in systemic TNF, and there were only modest differences between the rHb and the vehicle groups at LPS challenge doses of 2.5 and 20 mg/kg, whereas no difference was observed at the 10 mg/kg concentration. At LPS concentrations below 10 microg/kg, the increases in circulating TNF were dose dependent and no differences were observed in serum TNF levels between the rHb1.1 and vehicle groups. In addition, there were generally no differences in IL-6 levels between the experimental groups, although at 10 mg/kg LPS, a twofold increase in plasma IL-6 levels over those in the controls was observed in the rHb1.1-treated animals. Infusion of rHb1.1 alone did not induce any increase in circulating IL-6 or TNF. These data demonstrate that endotoxin exacerbation, although apparent, was observed only at the highest doses of LPS and that at lower concentrations, there were no differences in the extent of cytokine elevation or in survival rate when rHb1.1-, albumin-, or vehicle-pretreated animals were compared.
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PMID:Interactions of recombinant hemoglobin (rHb1.1) and endotoxin in vivo: effects on systemic tumor necrosis factor and interleukin-6 levels in lethal and sublethal murine models of endotoxemia. 935 82

Epidemiologic and occupational studies indicate adverse health effects due to inhalation of particulate air pollutants, but precise biologic mechanisms responsible have yet to be fully established. The tracheobronchial epithelium forms the body's first physiologic barrier to such airborne pollutants, where ciliary movement functions to remove the offending substances caught in the overlying mucus layer. Resident and infiltrating phagocytic cells also function in this removal process. In this paper, we examine the role of reactive oxygen and nitrogen species (ROS/RNS) in the response of airway epithelium to particulates. Some particulates themselves can generate ROS, as can the epithelial cells, in response to appropriate stimulation. In addition, resident macrophages in the airways and the alveolar spaces can release ROS/RNS after phagocytosis of inhaled particles. These macrophages also release large amounts of tumor necrosis factor alpha (TNF-alpha), a cytokine that can generate responses within the airway epithelium dependent upon intracellular generation of ROS/RNS. As a result, signal transduction pathways are set in motion that may contribute to inflammation and other pathobiology in the airway. Such effects include increased expression of intercellular adhesion molecule 1, interleukin-6, cytosolic and inducible nitric oxide synthase, manganese superoxide dismutase, cytosolic phospholipase A2, and hypersecretion of mucus. Ultimately, ROS/RNS may play a role in the global response of the airway epithelium to particulate pollutants via activation of kinases and transcription factors common to many response genes. Thus, defense mechanisms involved in responding to offending particulates may result in a complex cascade of events that can contribute to airway pathology.
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PMID:The role of reactive oxygen and nitrogen species in the response of airway epithelium to particulates. 940 Jul 42

The correlation between haemodynamic and oxymetric parameters, and circulating cytokines has been little studied for the early phase of extensive burns. The aim of this prospective study was to evaluate survival, looking at variations in cardiac index (CI), oxygen delivery (DO2I) and consumption (VO2I) indexed to the body surface area (BSA), and circulating interleukin-6 (IL6) levels in the acute stage of major burns. Over a 12-month period, all patients admitted within 6 h of extensive thermal injury with total burn surface area (TBSA) of over 60 per cent, necessitating standardized resuscitation and mechanical ventilation, were included. Routine intensive care monitoring, including pulmonary and femoral artery catheters, was set up. During the first 3 days post-injury haemodynamic and oxymetric profiles were recorded every 6 h. Circulating IL6 samples were taken within 6 h of admission, then daily (at 24, 48 and 72 h). A comparison of the results in survivors (S) and non-survivors (NS) at those previously determined times was made. Ten consecutive patients were studied. Six patients survived (Age = 33 +/- 10 years; TBSA = 76 +/- 11 per cent) and four died (Age = 40 +/- 14 years; TBSA = 77 +/- 13 per cent). Similar initial hypovolemic profiles were found in both groups. From 24 h, a hyperdynamic status was observed which increased until 72 h. This hyperkinetic evolution was more marked in the survivors (CI: 4.6 +/- 2.0 for NS and 6.9 +/- 1.51 min-1 m-2 for S; SVRI: 2125 +/- 1288 for NS and 918 +/- 232 dyne s cm-5 m2 for S at 72 h). DO2I and VO2I were always higher in the survivors. DO2I and VO2I increased from admission to 72 h in the survivors whereas a significant drop in DO2I and VO2I occurred in the non-survivors at 48 h (DO2I:536 +/- 222 for NS and 1228 +/- 268 ml min-1 m-2 for S; VO2I:120 +/- 50 for NS and 251 +/- 56 ml min-1 m-2 for S (P < 0.01)). Plasma IL6 revealed abnormal values with consistent peaks at 24-48 h in the survivors (respectively 17,411 +/- 24,542 and 10,746 +/- 11,802 pg ml-1) and only moderate peaks in the non-survivors (865 +/- 652 and 912 +/- 485 pg ml-1). Finally, CI, DO2I, VO2I and circulating IL6 were always higher, and SVRI lower, in the survivors than in the non-survivors. The ability to increase DO2 and to optimize VO2 during the 'turning point' of 48 h seems to improve the prognosis of critically burned patients: the role of IL6 in this systemic inflammatory response is discussed.
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PMID:In the early stage of major burns, is there a correlation between survival, interleukin-6 levels and oxygen delivery and consumption? 942 13


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