Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.37 (neutrophil elastase)
 4,078 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple organ dysfunction syndrome (MODS) is a critical condition developing in the patients under overwhelming surgical insults such as a major surgery, severe trauma, extensive burn, and systemic sepsis. The host response to those surgical insults is the main pathogenetic factor contributing to the development of shock and MODS seen in surgical patients. The proinflammatory cytokines, TNF-alpha (TNF) and interleukin-1 beta (IL-1), are known to play a pivotal role in the pathogenetic mechanisms of MODS. In response to surgical insults, macrophages produce and release TNF and IL-1 which subsequently induce the production of other cytokines (IL-6, IL-8, etc.) and other endogenous chemical mediators (growth factors, adhesion molecules, complement cleavage products, thrombin, eicosanoids, PAF, nitric oxides, oxygen-free radicals, granulocyte elastase, etc.) The resultant systemic inflammation may develop into shock and MODS when the primary insults are overwhelming (early MODS) or a second inflammatory insult such as sepsis triggers an exaggerated inflammation. In the patients suffering from MODS, a systemic release of various cytokines is not properly regulated, and the high blood levels of the proinflammatory cytokines induce an autodestructive generalized inflammatory reaction. This condition is termed "Cytokine Storm" by the author. In the cytokine storm, not only proinflammatory cytokines but also anti-inflammatory cytokines are elevated in the blood stream. With the recent understanding of the biological and pathological roles of cytokines and other mediators, a new therapeutic strategy has been developed. In addition to the reduction of the surgical insults, a variety of anti-cytokine therapy and anti-mediator therapy has been tested in an attempt to prevent or treat the life-threatening MODS.
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PMID:[Cytokine storm in the pathogenesis of multiple organ dysfunction syndrome associated with surgical insults]. 894 Jun 90

In order to elucidate the role of interleukin 8 (IL-8) on the development of chronic lung disease (CLD) in neonates following an episode of respiratory distress syndrome (RDS), serial and simultaneous measurements of the concentration of IL-8 and granulocyte elastase alpha 1 proteinase inhibitor complex (E-alpha 1 PI) in the tracheobronchial aspirate of very low birthweight infants with RDS were conducted. The concentration of IL-8 and E-alpha 1 PI in infants with CLD was low in the first 48 h of life, but dramatically increased after 48 h. The concentration of IL-8 between 48 h of life and day 5 was significantly correlated to the fraction of inspired oxygen concentration (FiO2) within 48 h of age, but not to the mean airway pressure. Interleukin 8 seemed to stimulate neutrophils to release granulocyte elastase which, in turn, caused lung tissue injury, resulting in the development of CLD. It is suggested that high FiO2 is an important factor causing IL-8 production in the lung.
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PMID:Interleukin 8 and granulocyte elastase alpha 1 proteinase inhibitor complex in the tracheobronchial aspirate of infants with chronic lung disease following respiratory distress syndrome. 894 99

Neutrophils are reported to be a major factor in the pathogenesis of the adult respiratory distress syndrome (ARDS). We measured serial levels of circulatory interleukin (IL)-8 and neutrophil elastase in 16 patients with ARDS at the onset, on day 3 and on day 7 and studied the relationship of these levels to the clinical course. Circulatory IL-8 levels of all the patients at the onset were significantly elevated compared with controls, mean +/- SE, 30.0 +/- 6.7 pg/ml and 3.3 +/- 0.3 pg/ ml, respectively. There was a significant correlation between IL-8 and neutrophil elastase levels at the onset (r = 0.65, p < 0.01). In nonsurvivors circulatory IL-8 levels were significantly higher than those of survivors throughout the study. There were significant differences in oxygenation, as reflected by PaO2/FIO2 ratios, between survivors and nonsurvivors at day 7, mean +/- SE, 208.5 +/- 21.9 and 113.5 +/- 9.6, respectively. In conclusion, we have shown that the level of circulatory IL-8 is elevated in patients with ARDS, and sustained high levels of circulatory IL-8 might be correlated with a poor outcome.
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PMID:Sustained high levels of circulatory interleukin-8 are associated with a poor outcome in patients with adult respiratory distress syndrome. 896 89

The influence of cytokines on the inflammatory response in surgery has recently been the subject of investigations. We measured tumor necrotic factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and granulocyte elastase (GEL) in 26 patients undergoing elective cardiac operations using cardiopulmonary bypass (CPB), preoperatively, immediately after CPB, and on post-operative days (PODs) 1, 3, and 6. To evaluate the effect of these cytokines on pulmonary function, the patients were divided according to whether the oxygenation index (OI) on POD 1 was > 250 or < 250, into groups A and B, respectively. TNF-alpha and IL-1 beta were undetectable and there were no significant differences in the preoperative IL-6, IL-8, and GEL levels. However, immediately following CPB, the mean IL-6, IL-8 and GEL levels in both groups were significantly higher than the preoperative levels (P < 0.01). Moreover, all these levels were significantly higher in group B than in group A, at 162 +/- 150 pg/ml vs 64 +/- 53 pg/ml (P < 0.05) for IL-6; 53 +/- pg/ ml vs 22 +/- 20 pg/ml (P < 0.01) for IL-8; and 2477 +/- 1642 mg/ l vs 1397 +/- 774 mg/l (P < 0.01) for GEL. The IL-6 levels returned to the preoperative values in both groups on POD 1; however, the GEL levels remained significantly higher in group B than in group A postoperatively, at 616 +/- 326 mg/l vs 378 +/- 70 mg/l on POD 1, and at 292 +/- 70 mg/l vs 218 +/- 62 mg/ l on POD 3 (P < 0.05). Thus high levels of cytokines such as IL-6, IL-8, and GEL may be detrimental to respiratory function.
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PMID:Relationship between respiratory distress and cytokine response after cardiopulmonary bypass. 906 2

Cytokine levels during infection and sepsis have been extensively studied in the past. In contrast to the excellent data on tumour necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), and polymorphonuclear (PMN) granulocyte elastase (PMN-E) concentrations in blood, little is known about cytokine and PMN-E levels in tissue or local fluids like abdominal exudate in secondary, purulent peritonitis of man. Therefore, the authors studied perioperative intra-abdominal levels of TNF-alpha, IL-8 and PMN-E in 21 patients with severe purulent peritonitis. The average pre-operative levels of TNF-alpha were 694 +/- 239 pg/ml in exudate and 26 +/- 6 pg/ml in plasma, for IL-8 100 +/- 34 ng/ml and 0.7 +/- 0.5 ng/ml, and for PMN-E 68 +/- 14 microg/ml and 0.7 +/- 0.1 microg/ml, respectively. Standard surgical procedures reduced the intra-abdominal concentrations of cytokines and PMN-E to as low as one tenth of the pre-operative levels. Postoperatively, TNF-alpha and IL-8 levels recovered rapidly and pre-operative levels of IL-8 were reached again after 1 h and for TNF-alpha after 8 h. PMN-E concentration remained below the initial baseline within 8 h of observation. TNF-alpha concentration, but not IL-8 or PMN-E, depended on the microbiological load of the abdominal exudate (< or > 10(3) cfu/ml). There were no significant differences in the intra-abdominal or plasma levels of cytokines or PMN-E between survivors and non-survivors at any observation time.
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PMID:Perioperative pattern of peritoneal interleukin 8, tumour necrosis factor-alpha, and granulocyte elastase release in human secondary peritonitis. 911 38

Infectious complications are the leading cause of death in acute pancreatitis. Individual factors of immune defence could be of significance, whether or not a patient develops a severe course with infectious complications. In a prospective 5-year trial including 72 patients, we investigated 29 cellular and humoral markers of the body's defence system for their potential to indicate the severity and course of acute pancreatitis. Complement factors C3 and C4 as well as immunoglobulins IgG, IgM and IgA were normal, in general. Measurable levels of IL-1 alpha, IL-1 beta, IL-2 and sIL-2R could be detected only occasionally. Values of alpha 1-AT, TNF-alpha, TNF alpha-Rp75, neopterin, sICAM-1, IL-8, IL-1RA and sIL-6R did not correlate with a severe course. Due to the high magnitude of increase, CRP, IL-6 and granulocyte elastase were the best indicators of the inflammatory process. Delayed-type hypersensitivity response was the only early predictor of a severe course. It was superior over other cellular markers such as monocyte count or CD4+/CD8+ ratio. In vitro function of polymorphonuclear granulocytes (PMN) was not adequate to the severity of the disease already during the first week of illness. During further course, PMN motility and capacities to produce reactive oxygen species even worsened. The compromized PMN function could explain the frequent development of infectious complications in patients suffering from severe pancreatitis. These results should encourage new concepts of infection prophylaxis using stimulants of cellular defence.
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PMID:[Cellular and humoral functions in acute pancreatitis]. 913

Neutrophils play an important role in inflammatory processes in the lung and may cause tissue injury through, for example, release of proteinases such as neutrophil elastase. In addition to neutrophil elastase, stimulated neutrophils also release small nonenzymatic and cationic polypeptides termed defensins. The aim of the present study was to investigate whether defensins induce interleukin (IL)-8 expression in cells of the A549 lung epithelial cell line and in human primary bronchial epithelial cells (PBEC). Supernatants of defensin-treated A549 cells contained increased neutrophil chemotactic activity (16-fold) that was inhibited by antibodies against IL-8. Concurrently, within 3 and 6 h, defensins significantly increased the IL-8 levels in supernatants of both A549 cells (n = 6, P < 0.05 and P < 0.01, respectively) and PBEC (n = 4, P < 0.001 and P < 0.001, respectively). This defensin-induced increase was fully inhibited by the serine proteinase inhibitor alpha 1-proteinase inhibitor. In addition, defensins also increased IL-8 mRNA levels (12-fold); this increase was dependent on de novo mRNA synthesis and did not require protein synthesis. Furthermore, defensins did not affect IL-8 mRNA stability, indicating that the enhanced IL-8 expression was due to increased transcription. Our findings suggest that defensins, released by stimulated neutrophils, stimulate IL-8 synthesis by airway epithelial cells and thus may mediate the recruitment of additional neutrophils into the airways.
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PMID:Effect of defensins on interleukin-8 synthesis in airway epithelial cells. 917 53

To elucidate the mechanism of the development of chronic lung disease (CLD) in infants without respiratory distress syndrome or intra-uterine infection, we serially measured the concentrations of interleukin 8 (IL-8) and granulocyte elastase alpha 1 proteinase inhibitor complex (E-alpha 1 PI) and elastase activity in the tracheobronchial aspirate of very low birth weight infants without respiratory distress syndrome or intra-uterine infection until day 28. IL-8 concentration and elastase activity between day 21 and 28 in infants who developed CLD later were significantly higher compared with those in infants who did not develop CLD. E-alpha 1 PI concentration between day 25 and 28 in infants who developed CLD later was significantly higher compared with those in infants who did not develop CLD. The area under the curve of the IL-8 and E-alpha 1 PI concentrations and elastase activity between day 1 and day 28 in infants with CLD was significantly higher than those in infants without CLD. These data suggest that the lung tissue injury caused by the enzymes from neutrophils accumulated and activated by IL-8 also play an important role in the development of this type of CLD.
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PMID:Interleukin 8 and granulocyte elastase in the tracheobronchial aspirate of infants without respiratory distress syndrome or intrauterine infection and development of chronic lung disease. 931 87

Neutrophils play an important role in host defense by phagocytosing and destroying invading bacteria. A recent investigation revealed that glutamine (Gln) augmented the in vitro bactericidal activity of neutrophils from burn patients. However, it is unclear whether Gln enhances the function of neutrophils in postoperative patients. This study was designed to investigate the effect of Gln on the in vitro Escherichia coli-killing activity of neutrophils from postoperative patients. Nine randomly selected patients were included in this study. On the morning of the first postoperative day, blood was drawn and neutrophils were isolated. Eight healthy volunteers served as controls. E. coli was opsonized with pooled normal serum. Neutrophils (5 x 10(6)), together with opsonized E. coli (5 x 10(5)), were incubated for 2 h at 37 degrees C in Hanks' balanced salt solution supplemented with 0, 100, 500, or 1000 nmol/mL of Gln. The bactericidal function of neutrophils was determined by counting the number of viable bacteria. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, and granulocyte elastase levels in the cell culture supernatant were measured. Plasma C-reactive protein (CRP), cortisol, and amino acids were also analyzed. The plasma concentration of Gln was significantly lower in the postoperative patients than in the controls. Following culture with patient neutrophils, the number of viable E. coli decreased by 26% as the in vitro Gln concentration was increased from 500 to 1000 nmol/mL (P < 0.01). We defined the Gln 1000/Gln 500 ratio of the number of viable bacteria as the number of viable E. coli at an in vitro Gln concentration of 1000 nmol/mL divided by the number of viable E. coli at an in vitro Gln concentration of 500 nmol/mL. A positive correlation was thus demonstrated between the plasma Gln level and the Gln 1000/Gln 500 ratio of the number of viable bacteria in the patients (r = 0.69, P = 0.04). This finding indicated that as plasma Gln fell, there was an enhancement of neutrophil E. coli-killing activity by neutrophils in in vitro tests when the Gln concentration was increased from 500 to 1000 nmol/mL. Gln supplementation caused no appreciable changes in TNF-alpha, IL-1 beta, IL-8, or granulocyte elastase levels in cell culture supernatants. A negative correlation was recognized between the patient plasma Gln level and the Gln 1000/Gln 500 ratio of the cell culture supernatant IL-8 level (r = -0.73, P = 0.025). In conclusion, Gln supplementation enhanced the in vitro bactericidal function of neutrophils from postoperative patients.
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PMID:Glutamine-enhanced bacterial killing by neutrophils from postoperative patients. 935 31

The objective of our study was to elucidate the involvement of interleukin (IL)-8 in the hCG-induced rabbit ovulatory process. After administering hCG (100 IU i.v.), we examined myeloperoxidase (MPO) activity, which represents neutrophil accumulation; neutrophil elastase (NE) activity, which is an indicator of neutrophil activity; and levels of IL-8 in the ovaries. The maximal level of IL-8 was observed before MPO and NE activities reached a peak: production of IL-8, MPO, and NE activities peaked, respectively, at 4 h (5.58 +/- 0.88 pg/mg ovary, n = 13), 6 h (1.07 +/- 0.13 deltaA/min per gram ovary, n = 8), and 9 h (18.89 +/- 1.05 U/g ovary, n = 8). Anti-rabbit IL-8 antiserum given i.v. significantly reduced the maximal levels of hCG-induced MPO activity (antiserum vs. control; 0.34 +/- 0.04 vs. 1.12 +/- 0.11 deltaA/min per gram ovary, n = 14, p < 0.001) and NE activity (8.14 +/- 0.85 vs. 18.30 +/- 0.79 U/g ovary, n = 14, p < 0.001). The hCG-induced ovulation rate was significantly inhibited by the antiserum (50.5% vs. 83.9%, n = 14, p < 0.001). Intraperitoneal injection of 100 mg/kg of ONO-5046, a specific NE inhibitor, also attenuated the ovulation rate (ONO-5046 vs. vehicle; 56.0% vs. 74.0%, n = 14, p < 0.05). These findings clearly indicate that IL-8 has an important role in the hCG-induced ovulatory process through the accumulation and activation of neutrophils.
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PMID:Interleukin-8 as an essential factor in the human chorionic gonadotropin-induced rabbit ovulatory process: interleukin-8 induces neutrophil accumulation and activation in ovulation. 947 10


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