Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on the knowledge that neutrophil elastase (NE) in cystic fibrosis (CF) epithelial lining fluid (ELF) can induce human bronchial epithelial cells to express the gene for interleukin 8 (IL-8), an 8.5-kD neutrophil chemoattractant, we have evaluated CF ELF for the presence of IL-8, and investigated the ability of aerosolized recombinant secretory leukoprotease inhibitor (rSLPI) to suppress NE, and hence IL-8, levels on the respiratory epithelial surface in CF. Enzyme-linked immunoassay revealed 21.9 +/- 4.8 nM IL-8 in CF ELF compared with none in normals. Active NE was detectable in ELF of all individuals with CF and was significantly decreased (P < 0.03) after aerosolization of rSLPI. Human bronchial epithelial cells exposed to CF ELF recovered before rSLPI therapy expressed IL-8 mRNA transcripts, but ELF recovered after rSLPI therapy induced far less bronchial epithelial cell IL-8 gene expression. Consistent with this, rSLPI aerosol therapy caused a marked reduction in CF ELF IL-8 levels (P < 0.05) and neutrophil number (P < 0.02). There was also a clear association between CF ELF active NE and IL-8 levels (r = 0.94). These data suggest that rSLPI therapy not only suppresses respiratory epithelial NE levels, but also breaks a cycle of inflammation on the CF epithelial surface.
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PMID:Modulation of airway inflammation in cystic fibrosis. In vivo suppression of interleukin-8 levels on the respiratory epithelial surface by aerosolization of recombinant secretory leukoprotease inhibitor. 135 2

The neutrophil enzyme elastase is a potent secretagogue of airway secretory cells, and elastase is present in high concentrations in sputum of patients with hypersecretion (e.g., cystic fibrosis, bronchiectasis). Interleukin-8 (IL-8), a recently discovered cytokine with potent neutrophil chemotactic properties in vitro, is also found in the sputum of these patients. We used an isolated tracheal segment in dogs in vivo to study the effect of IL-8 in causing neutrophil accumulation, elastase release, and secretion (by measuring lysozyme concentrations) in the luminal superfusate. IL-8 caused a potent time-dependent neutrophil accumulation at between 3 and 6 h. The effect was significant at 10(-9) and maximum at 10(-8) M. No increase in free elastase, cathepsin G, or lysozyme was detected in the superfusate. Thus, in contrast to previous studies showing that ragweed antigen causes the accumulation of neutrophil elastase which in turn causes lysozyme secretion, IL-8 causes neutrophil accumulation without granule secretion (or subsequent secretagogue activity). The findings were confirmed with dog and human neutrophils in vitro.
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PMID:Interleukin-8 induces neutrophil accumulation but not protease secretion in the canine trachea. 147 6

The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators in respiratory epithelial lining fluid (ELF) of CF individuals might induce IL-8 production by epithelial cells, thus recruiting neutrophils to the airways. BET-1A human bronchial epithelial cells at rest or incubated with normal ELF showed little IL-8 gene expression, but after incubation with CF ELF, a marked increase in IL-8 transcript levels was observed. CF ELF contained high levels of neutrophil elastase (NE) and various serine protease inhibitors prevented CF ELF from inducing IL-8 gene expression in BET-1A cells, suggesting that NE was the dominant inducer for IL-8 production in CF ELF. The addition of purified NE caused BET-1A cells to increase IL-8 gene transcription with accumulation of mRNA transcripts and to release IL-8-like neutrophil chemotactic activity. These observations suggest a self-perpetuating inflammatory process on the CF bronchial surface where NE released by neutrophils induced the bronchial epithelium to secrete IL-8, which in turn recruits additional neutrophils to the bronchial surface.
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PMID:Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. 156 86

A hyperdynamic sepsis model was set up in seven adult baboons to evaluate neutrophil-activating peptide-1/interleukin (IL)-8 (NAP-1/IL-8), IL-1 beta, IL-6, tumor necrosis factor-alpha (TNF alpha), and IFN-gamma in plasma. By continuous intravenous administration of 10(10) cfu/kg live Escherichia coli over 8 h with additional infusion therapy (less than or equal to 50 ml/kg/h), endotoxin plasma levels of 2.7-22.3 ng/ml were observed. In plasma the kinetics of NAP-1/IL-8 and IL-6 were similar to those of IL-1 at the end of the experiment (8 h) (peak median values, 34, 4197, and 230 ng/ml, respectively). Differences were greatest for IL-6. Monocyte activation during sepsis was confirmed by elevated plasma neopterin levels (91-139 mumol/mmol of creatine). Granulocyte activation was evident from both incipient neutropenia and the massive release of neutrophil elastase into the plasma as measured by a new immunoassay (peak level, 374 ng/ml). Thus, in primate bacteremia, early TNF release is followed by a concomitant increase of NAP-1/IL-8 with plasma kinetics similar to those of IL-6 and IL-1 and accompanied by massive activation of neutrophils.
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PMID:Plasma neutrophil-activating peptide-1/interleukin-8 and neutrophil elastase in a primate bacteremia model. 190 12

We used a whole-gut perfusion technique to study subclinical gut inflammation in children with cystic fibrosis (18 elective tests, three lavages to treat distal intestinal obstruction syndrome); and in 12 control children with constipation or pre-colonoscopy. We assayed for haemoglobin, IgG, albumin, alpha-1-antitrypsin, granulocyte elastase, interleukin-1 beta (IL-1 beta) and IL-8 concentrations in whole-gut lavage fluid. Results for two children with distal intestinal obstruction syndrome, the only children in the series taking Nutrizym 22, were strikingly abnormal. This new test has revealed subclinical gut mucosal inflammation in a minority of CF children, for which distal intestinal obstruction syndrome, Nutrizym 22 treatment, or both, may be risk factors.
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PMID:Gut inflammation in children with cystic fibrosis on high-dose enzyme supplements. 856 82

The objective of this study was to evaluate and compare the derangement of body homeostatis and the inflammatory response after different types of traumatological operations in patients with multiple injuries. These were determined in a total of 60 operations. The procedures comprised osteosynthesis of the femur (n = 28), the pelvic girdle (n = 11) the spine (n = 8), and facial and basal skull reconstructions (n = 13). Specific and unspecific parameters of the inflammatory response were determined on the morning of the operation, immediately after the procedure, every 6 h on the 1st day and 48 h after the end of surgery. After all types of operations (pelvis, femur, spine, face/basal skull) significant alterations were observed for neutrophil elastase, C-reactive protein, interleukin 6, interleukin 8, antithrombin III, partial thromboplastin time and other parameters. The degree of postoperative changes differed significantly (Kruskal-Wallis test, P < 0.05) among the four types of operations for lactate, heart rate, PO2/FiO2 ratio and nitrogen excretion and showed a strong discriminating tendency for neutrophil elastase and C-reactive protein. The changes were most pronounced after operations on the pelvic girdle, followed by procedures in the femoral, spinal, and facial/basal skull regions. We conclude that a considerable inflammatory response and pronounced disturbance of body homeostasis follow traumatological operative procedures, varying in severity with the type of surgery. Several parameters allow quantitation of the surgical trauma and differentiation between different operations/regions. Further research should focus on the interrelationship between pre-existing preoperative inflammation and the additional trauma inflicted by surgery in patients with severe injuries.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Postoperative homeostatic imbalance after trauma surgical interventions of various degrees in polytrauma]. 748 29

CD43, an anionic rod-like mucin molecule on white blood cells, is thought to provide a barrier that prevents interactions of other surface molecules and acts as negative regulator of cell function. As a correlate, CD43 is expected to be altered or down-regulated when blood cells are functionally activated. This study examines CD43 of blood neutrophils before and after treatment with known activating agents. Flow cytometry indicated that PMA and A23187, and to a much lesser extent, FMLP and IL-8, decrease neutrophil expression of CD43. Two separate mechanisms were identified for CD43 down-regulation. Both are proteolytic processes. PMA-induced down-regulation is a rapid process involving proteolysis at a minimum of two sites, one within the N-terminal distal region recognized by mAbs and the other at a membrane-proximal site. The PMA-induced protease, cd43' ase, is characterized by insensitivity to DFP, TLCK, leupeptin, pepstatin, and 1,10 phenanthroline (< 5 mM). PMA-induced CD43 down-regulation is extensive but never complete, terminating at approximately 10 min after down-regulating 65 to 85% of molecules, and thereby converting neutrophils from dense to sparse CD43 expression. The second CD43 down-regulation mechanism, although likely a regulated event in vivo, occurred slowly in this study in neutrophils incubated without additives; the process is not affected by PMA, involves the action of a DFP-sensitive protease, releases N-terminal mAb-reactive fragments of 52 kDa or 40 kDa and can be mimicked by exogenous neutrophil elastase. The complexity and apparent tight regulation described here for the two down-regulatory mechanisms are consistent with an important role for CD43 in preventing or dampening cell surface interactions of blood neutrophils.
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PMID:Two proteolytic pathways for down-regulation of the barrier molecule CD43 of human neutrophils. 751 53

Bronchopulmonary disease in patients with cystic fibrosis (CF) is a paradigm of neutrophil-dominated airway inflammation. We hypothesized that proinflammatory cytokines contribute to a localized neutrophil-dominated inflammatory state as present in CF airways. In a cross-sectional study, we analyzed 63 sputum samples from 33 CF patients for concentrations of the cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-8, tumor necrosis factor-alpha (TNF-alpha), and granulocyte-colony stimulating factor (G-CSF) by means of enzyme-linked immunosorbent assay. Furthermore, the activity of neutrophil elastase (NE) in the sputum samples was determined using a specific chromogenic substrate. Compared to sputum samples from 10 healthy controls, there were significantly increased concentrations of IL-1 beta, IL-8 and TNF-alpha in the CF sputum samples. The concentration of IL-8 correlated significantly with NE activity in the CF sputum samples. In CF patients with airways chronically colonized with Pseudomonas aeruginosa, IL-8 concentrations in sputum were significantly enhanced. In glucocorticoid-treated patients, IL-1 alpha and G-CSF sputum concentrations were significantly lower when compared to levels in the other patients. These results show that there are high concentrations of proinflammatory cytokines in CF airways which may contribute to the localized neutrophil-dominated inflammatory state found clinically.
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PMID:Cytokines in neutrophil-dominated airway inflammation in patients with cystic fibrosis. 753 67

We determined the plasma concentrations of interleukin 8 (IL-8), polymorphonuclear leukocyte elastase (PMNE), and endotoxin in patients with septic shock in order to investigate the role of IL-8 and PMNE in the development of septic shock, especially in septic adult respiratory distress syndrome (ARDS). The IL-8 concentration in patients with septic shock was 6.28 +/- 9.00 ng/mL (mean +/- SD, n = 29), which was significantly higher (P < 0.0001) than the concentration in septic patients without shock (0.35 +/- 0.35 ng/mL, n = 40). There was a significant correlation between the IL-8 concentration and the PMNE concentration at the onset of septic shock (r = 0.6916, P < 0.0001). The IL-8 concentration was also significantly correlated with the endotoxin concentration (r = 0.5584, P = 0.0016). There was a significant negative correlation (r = -0.8237, P < 0.0001) between the serum PMNE concentration and the oxygenation index (PaO2/FiO2) at the onset of septic shock. These results indicate that IL-8 and PMNE are produced in large quantities when septic shock occurs, and may play a role in the development of septic ARDS.
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PMID:Plasma interleukin 8 and polymorphonuclear leukocyte elastase concentrations in patients with septic shock. 758 59

We estimated defensins, antimicrobial and cytotoxic peptides localized in azurophil granules of neutrophils, in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB). BALF from DPB patients contained a higher concentration of defensins than those from patients with idiopathic pulmonary fibrosis and healthy volunteers. A significant correlation was observed between the concentration of defensins and the number of neutrophils, the concentration of interleukin-8 or neutrophil elastase in BALF of DPB patients. An immunohistochemical defensins in neutrophils and mucinous exudates in the airways and in the surface of bronchiolar epithelial cells. After treatment with macrolide antibiotics, significant reductions in the concentrations of defensins, IL-8 and neutrophil numbers in BALF of DPB patients were observed. These findings suggest that the lung injury in DPB could be caused by defensins released by neutrophils accumulated in the airways.
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PMID:[A study of defensins in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis]. 759 98


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