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)

Cardiopulmonary bypass has been implicated in triggering a multisystem inflammatory response caused by blood contact with the artificial surfaces of the circuit. This leads to increased morbidity levels because of cytotoxic enzymes released from activated neutrophils. Recently, it was discovered that certain inflammatory mediators are permeable to the membrane of the hemoconcentrator. As a result, this study was undertaken to quantitatively characterize the nature of this movement by deriving a sieving coefficient (S) for four inflammatory mediators: myeloperoxidase, elastase, interleukin-6, and lactoferrin. The results show no permeability through the hemoconcentrator for the two neutrophil derived enzymes myeloperoxidase and elastase (S = 0, p > 0.05). Conversely, although larger than the pore size of the hemoconcentrator, lactoferrin sieves through unrestricted (S = 1.030 +/- 0.037, p < 0.0001). Interleukin-6 is removed in concentrations greater than those found in the blood, which yields a sieving coefficient significantly greater than 1.0 (S = 1.246 +/- 0.042, p < 0.0001). In addition to sieving coefficients, this study offers theories as to why these mediators acted as such. One conclusion is that certain mediators are efficaciously removed by the hemoconcentrator and, with additional study, may result in an attenuated inflammatory response.
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PMID:Derivation of sieving coefficients to determine the efficacy of the hemoconcentrator in removal of four inflammatory mediators produced during cardiopulmonary bypass. 915 85

Bioactive substances in fresh frozen plasma (FFP) are considered to be related to adverse reactions after transfusion, particularly in septic or traumatized patients. Therefore, we analysed the concentration of various bioactive substances (histamine, eosinophil cationic protein, eosinophil protein X, myeloperoxidase and interleukin-6) in 25 u. of thawed FFP from healthy donors. These were compared with donor plasma concentrations of 24 healthy controls. In addition, we analysed the concentration of the bioactive substances, except interleukin-6, in 25 u. of thawed FFP, which were subjected to leucocyte filtration before freezing and storage. Finally, we analysed the substances in 10 leucocyte non-filtered plasma units before freezing and storage, and after thawing, respectively. Before analyses, which were performed by ELISA and RIA methods, these latter samples were sterile filtered through a 0.20-micron filter. Histamine, eosinophil cationic protein, eosinophil protein X and myeloperoxidase concentrations were significantly greater (P < 0.05) in the 25 u. of FFP compared with normal donor plasma. Pre-storage leucocyte filtration reduced concentrations of the bioactive substances in FFP to concentrations comparable with normal donor plasma concentrations. Interleukin-6 was undetectable in all FFP units and in 21 of the 24 control donors. Histamine, eosinophil cationic protein and myeloperoxidase concentrations were significantly higher (P < 0.05) in samples collected from the 10 u. of FFP after freezing and thawing compared with samples collected before freezing. We conclude that fresh frozen plasma prepared by a conventional separation method contains various leucocyte-derived bioactive substances, which may be reduced by pre-storage leucocyte filtration.
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PMID:Leucocyte-derived bioactive substances in fresh frozen plasma. 917 70

1. To address the question of whether endotoxaemia could be involved in the inflammatory response induced by long-term strenuous exercise, 18 male marathon runners [mean age 41 +/- 2 (SEM) years] were studied. Their performance in the marathon ranged from 2 h 46 min to 4 h 42 min. 2. Four venous blood samples were drawn: at rest, just before the race (baseline); within 15 min following the completion of the marathon; after 1 h of recovery; and the morning after the race. 3. The following humoral markers of the inflammatory response to exercise were measured: polymorphonuclear myeloperoxidase (MPO), anaphylatoxin C5a (C5a), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Plasma endotoxin was measured by a sensitive and rapid chromogenic Limulus assay. All inflammatory markers were significantly increased (P < 0.001) after the race, reaching in most cases peak values in the first blood sample drawn following the completion of the marathon [MPO, 298 +/- 19 ng/ml (SEM); C5a, 1.45 +/- 0.32 ng/ml; TNF-alpha, 20 +/- 3 pg/ml; IL-6, 88 +/- 13 pg/ml] when compared with baseline [MPO, 146 +/- 16 ng/ml (SEM); C5a, 0.27 +/- 0.2 ng/ml; TNF-alpha, 12 +/- 1.5 pg/ml: IL-6, 1.0 +/- 0.5 pg/ml]. Traces of plasma endotoxin (ranging from 5 to 13 pg/ml, with one exceptionally high value of 72 pg/ml measured in one runner) were detected in seven subjects within the first hour of recovery. An ELISA method was used to determine the endogenous IgG antibodies toward a range of Gram-negative bacterial lipopolysaccharides (LPSs) of different sizes and structures. A transient decrease in certain anti-LPS activities, mainly against rough LPS, occurred in most cases in the first blood sample drawn after the race. There was no correlation between the magnitude of the inflammatory response to exercise, as assessed by the increase in blood levels of humoral markers of inflammation, and the changes in circulating endotoxin levels of anti-LPS IgG activity following the race. 4. From these results, we conclude that the mild, transient endotoxaemia detected in some of our subjects does not play a major role in the observed inflammatory response to a marathon competition.
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PMID:Mild endotoxaemia and the inflammatory response induced by a marathon race. 917 42

Adverse reactions to transfusion of allogeneic blood may depend on content of leucocytes and platelets and on storage-time of the erythrocyte suspensions. Therefore, we studied the efficacy of prestorage leucocyte reduction by filtration on total content and extracellular accumulation of histamine, eosinophil cationic protein (ECP), eosinophil protein X (EPX), myeloperoxidase (MPO), plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in samples obtained from 5 units of SAGM blood, 7 units of plasma-reduced whole-blood and 6 units of whole-blood before and after filtration, respectively. In addition, we analysed supernatants from the same units after storage at +4 degrees C for 0, 21 and 35 d, respectively. The filtration was performed at room temperature within 2-4 h after donation. The substances were analysed by ELISA and RIA methods and we also analysed the donor plasma levels of the same bioactive substances. The total content of histamine, ECP, EPX, and MPO were 10-70-fold higher in all unfiltered erythrocyte products compared to donor plasma concentrations, while PAI-1 content was 15-20-fold higher only in plasma-reduced whole-blood and whole-blood. Prestorage leucocyte filtration significantly reduced the total histamine, ECP, EPX, MPO and PAI-1 content to levels similar to donor plasma levels in plasma-reduced whole-blood and whole-blood, while PAI-1 was still low in filtered SAGM blood. In addition, the levels of extracellular bioactive substances at d 0 after donation and filtration were within the range of concentrations in donor plasma, and there was no time-dependent accumulation during storage for 35 d at +4 degrees C. IL-6 was not detected in either plasma or samples obtained from the blood bags. These results suggest prestorage leucocyte filtration to deplete leucocyte contents to levels, which prevent the previously shown time-dependent accumulation of leucocyte derived bioactive substances in various erythrocyte suspensions. In addition, the PAI-1 results suggest leucocyte filters to reduce the obligatory platelet content in whole-blood products.
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PMID:Leucocyte and platelet-derived bioactive substances in stored blood: effect of prestorage leucocyte filtration. 918 39

There is now clear evidence supporting the role of cytokines in the clinical and immunopathological manifestations of human inflammotory bowel disease. The purpose of the present study was to determine the possible role of a cytokine network in a rat model of trinitrobenzene sulfonic acid-induced colitis and to examine its relation to intestinal permeability. After a rapid increase in the intestinal permeability of Evans blue in the colon, tumor necrosis factor-alpha increased transiently, and interleukin-1 and interleukin-6 followed thereafter. The majority of tumor necrosis factor-alpha- and interleukin-1-producing cells observed by immunofluorescent staining was revealed to be macrophages. Repeated injections of interleukin-1 receptor antagonist led to a modest decrease in myeloperoxidase activity and colon weight. These findings suggest that enhanced pro-inflammatory cytokine production from intestinal macrophages accompanied by increased intestinal permeability may contribute to intestinal and systemic features of trinitrobenzene sulfonic acid-induced colitis. Pharmacologic blockade of pro-inflammatory cytokines may help reduce intestinal inflammation.
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PMID:Role of cytokines in experimental colitis: relation to intestinal permeability. 924 23

Ten patients with perennial allergic rhinitis and 10 healthy subjects were studied to determine most discriminative nasal irrigation fluid marker(s) and to compare samples that were collected at baseline and over a 1-hour period, every 15 minutes. The latter were pooled and designated 1-hour sample. In the nasal irrigation we investigated the following inflammatory cells and soluble mediators: eosinophils, neutrophils, granulocyte-macrophage colony-stimulating factor, interleukin-4, interleukin-6, interleukin-8, ECP, EPX, MPO, leukotriene C4, leukotriene B4, prostaglandin E2, tryptase and fibrinogen. Patients with PAR were then treated for 2 weeks with the topical nasal steroid. The only marker that discriminated patients with perennial allergic rhinitis and healthy subjects was eosinophil count (EO%): correspondingly 14.01 +/- 5.8 and 0.18 +/- 0.09, (M +/- SD). Difference between the studied groups did not depend on the time of irrigation, baseline or 1-hour. EO% was also the only marker of a clinically successful treatment with the nasal steroid, 14.01 +/- 5.8 and 0.87 +/- 0.4, before and after treatment respectively. We conclude that EO% is the most sensitive inflammatory marker of perennial allergic rhinitis, and that baseline nasal irrigation can be used to study nasal mucosal inflammation.
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PMID:Clinical and nasal irrigation fluid findings in perennial allergic rhinitis. 943 56

There is a need for more insight into the pathogenesis of Streptococcus pneumoniae pneumonia, as the fatality rate associated with this disease remains high despite appropriate antibiotherapy. The host response to pneumococci was investigated after intranasal inoculation of CD1 mice with 10(7) log-phase CFU of bacteria. We identified five major pathogenesis steps from initial infection to death. In step 1 (0 to 4 h), there was ineffective phagocytosis by alveolar macrophages, with concurrent release of tumor necrosis factor alpha (TNF), interleukin-6 (IL-6), and nitric oxide (NO) in bronchoalveolar lavage (BAL) fluid, TNF, IL-6, and interleukin-1 alpha (IL-1) in lung tissues, and IL-6 in serum, which were associated with tachypnea and hemoconcentration. In step 2 (4 to 24 h), bacterial growth in alveoli and polymorphonuclear cell recruitment from bloodstream to lung tissue (high myeloperoxidase levels) to alveoli were associated with high release of all three cytokines and leukotriene B4 (LTB4) in tissue and BAL fluid, as well as transient spillover of IL-1 in serum. In step 3 (24 to 48 h), despite downregulation of TNF and IL-1 in BAL fluid and lungs, there was appearance of injury to alveolar ultrastructure, edema to interstitium, and increase in lung weight as well as regeneration of type II pneumocytes and increased secretion of surfactant; bacteria progressed from alveoli to tissue to blood, and body weight loss occurred. In step 4 (48 to 72 h), strong monocyte recruitment from blood to alveoli was associated with high NO release in tissue and BAL fluid, but there was also noticeable lymphocyte recruitment and leukopenia; bacteremia was associated with TNF and IL-6 release in blood and thrombocytopenia. In step 5 (72 to 96 h), severe airspace disorganization, lipid peroxidation (high malondialdehyde release in BAL fluid), and diffuse tissue damage coincided with high NO levels; there was further increase in lung weight and bacterial growth, loss in body weight, and high mortality rate. Delineation of the sequential steps that contribute to the pathogenesis of pneumococcal pneumonia may generate markers of evolution of disease and lead to better targeted intervention.
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PMID:Cytokine kinetics and other host factors in response to pneumococcal pulmonary infection in mice. 948 75

Eosinophils, prominent cells in asthmatic inflammation, have been shown to synthesize, store, and release an array of up to 18 cytokines and growth factors, including interleukin-6 (IL-6). In this report, we show that IL-6 immunofluorescence localizes to the matrix of the crystalloid granule in peripheral blood eosinophils from atopic asthmatics using confocal laser scanning microscopy (CLSM). Granule localization of IL-6 was confirmed using dot-blot analysis and enzyme-linked immunosorbent assay (ELISA) on subcellular fractions of highly purified eosinophils produced from density centrifugation across a 0% to 45% Nycodenz gradient. IL-6 was found to coelute with eosinophil crystalloid granule marker proteins, including eosinophil peroxidase (EPO), major basic protein (MBP), arylsulfatase B, and beta-hexosaminidase. Immunoreactivity to IL-6 colocalized with granule-associated IL-2 and IL-5 in subfractionated eosinophils. We also made the novel and compelling observation that interferon gamma (IFNgamma), a Th1-type cytokine, stimulated an early elevation in eosinophil IL-6 immunoreactivity. A 2.5-fold enhancement of IL-6 immunoreactivity in eosinophil granules was observed within 10 minutes of IFNgamma treatment (500 U/mL), as determined by subcellular fractionation and CLSM. These findings suggest that IFNgamma has short-term effects on human eosinophil function and imply that a physiologic role exists for Th1-type cytokine modulation of Th2-type responses in these cells.
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PMID:Intracellular localization of interleukin-6 in eosinophils from atopic asthmatics and effects of interferon gamma. 951 52

The presence of 2 million or more peroxidase-positive white blood cells per ml of semen, or the diagnosis of male accessory gland infection, is associated with important biochemical and biological changes in semen plasma and in the spermatozoa, reducing their fertilizing potential in vitro and in vivo (e.g., during intra-uterine insemination). In addition to the effects of reactive oxygen species, and its influence on the essential fatty acid composition of the sperm membrane, potentially unfavourable effects can occur through the intermediate of increased concentrations of certain cytokines, and decreased activity of enzymes such as alpha-glucosidase. In contrast, lower numbers of white blood cells may exert beneficial effects on spermatozoa thanks to the increased production of hepatocyte growth factor/scatter factor (a tissue repairing substance), and the stimulation of immuno-competent cells by particular cytokines (e.g., Interleukin-6).
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PMID:Mechanisms of sperm deficiency in male accessory gland infection. 962 40

Polymicrobial sepsis induced by cecal ligation and puncture (CLP) reproduces many of the pathophysiologic features of septic shock. In this study, we demonstrate that mRNA for a broad range of pro- and anti-inflammatory cytokine and chemokine genes are temporally regulated after CLP in the lung and liver. We also assessed whether prophylactic administration of monophosphoryl lipid A (MPL), a nontoxic derivative of lipopolysaccharide (LPS) that induces endotoxin tolerance and attenuates the sepsis syndrome in mice after CLP, would alter tissue-specific gene expression post-CLP. Levels of pulmonary interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), granulocyte colony-stimulating factor (G-CSF), IL-1 receptor antagonist (IL-1ra), and IL-10 mRNA, as well as hepatic IL-1beta, IL-6, gamma interferon (IFN-gamma), G-CSF, inducible nitric oxide synthase, and IL-10 mRNA, were reduced in MPL-pretreated mice after CLP compared to control mice. Chemokine mRNA expression was also profoundly mitigated in MPL-pretreated mice after CLP. Specifically, levels of pulmonary and hepatic macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, MIP-2, and monocyte chemoattractant protein-1 (MCP-1) mRNA, as well as hepatic IFN-gamma-inducible protein 10 and KC mRNA, were attenuated in MPL-pretreated mice after CLP. Attenuated levels of IL-6, TNF-alpha, MCP-1, MIP-1alpha, and MIP-2 in serum also were observed in MPL-pretreated mice after CLP. Diminished pulmonary chemokine mRNA production was associated with reduced neutrophil margination and pulmonary myeloperoxidase activity. These data suggest that prophylactic administration of MPL mitigates the sepsis syndrome by reducing chemokine production and the recruitment of inflammatory cells into tissues, thereby attenuating the production of proinflammatory cytokines.
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PMID:Pulmonary and hepatic gene expression following cecal ligation and puncture: monophosphoryl lipid A prophylaxis attenuates sepsis-induced cytokine and chemokine expression and neutrophil infiltration. 967 35


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