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)

Although numerous cytokines, including interleukin (IL)-1, IL-8, and tumor necrosis factor, circulate in critically ill patients at risk for acute respiratory distress syndrome (ARDS), none clearly predict the development of the syndrome. We hypothesized that cytokines, such as IL-1ra, IL-10, and IL-4, which modulate inflammation, might contribute to or reflect the development of acute lung injury. Accordingly, serial levels of IL-1ra and IL-10 were measured in 77 patients who were identifed as being at risk for the development of ARDS. Initial IL-1ra levels were significantly higher (p < 0.0001) in the patients (7.82 [2.29-38.01] ng/ml) than in normal control subjects (0.24 [0.24-0.34] ng/ml) but did not predict the development of ARDS. Initial IL-1ra levels, however, were greater (p = 0.038) in the patients who died (31.95 [3.02-65.06] ng/ml) compared with survivors (6.61 [1.86-29.33] ng/ml). Similarly, IL-10 levels were increased in patients (155 [53.75-318.75] ng/ml) compared with normal control subjects (0 ng/ml) but did not predict the development of ARDS. Like IL-1ra levels, initial IL-10 levels were significantly higher (p = 0.005) in patients who died compared with survivors. IL-4 was not detectable in any of the patient plasma samples measured. Thus, modulators of inflammation are increased in patients at risk for ARDS who die, but do not predict the development of the syndrome.
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PMID:Circulating IL-1ra and IL-10 levels are increased but do not predict the development of acute respiratory distress syndrome in at-risk patients. 910 96

We have herein established an endotoxemia-induced acute respiratory distress syndrome (ARDS)-like lung injury administered a sublethal dose of lipopolysaccharide (LPS) intravenously 36 hours after the intratracheal instillation of heat-killed Streptococcus pyogenes (OK-432). At 36 hours after OK-432 priming, a mild infiltration into the lungs, consisting of a small number of neutrophils and macrophages, was observed without destruction of pulmonary architecture. A subsequent challenge with a sublethal dose of LPS induced pathologic changes characteristic of ARDS--such as extensive edema in alveolar lumina, marked infiltration composed of a large number of neutrophils and a few macrophages, fibrin deposit in alveolar space, and destruction of pulmonary architecture--resulting in severe hypoxemia. Concomitantly, LPS challenge after priming with OK-432 induced a marked elevation of IL-8 levels in serum and bronchoalveolar lavage fluid with local IL-8 production in lungs, as revealed by immunohistochemical analysis. An anti-IL-8 antibody treatment almost completely prevented pulmonary edema, destruction of pulmonary architecture, and impairment in gas exchange as well as neutrophil infiltration in lungs; there was also a significant reduction in the rate of acute lethality. These results provide evidence that IL-8 has a pivotal role in the induction of ARDS associated with endotoxemia, probably by recruiting and activating neutrophils locally.
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PMID:Prevention of endotoxemia-induced acute respiratory distress syndrome-like lung injury in rabbits by a monoclonal antibody to IL-8. 912 Nov 20

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.
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PMID:TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria. 912 3

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

Chemokines contribute to the inflammatory response by selective attraction of various leukocytic cell types. Human GCP-2 was originally identified by amino acid sequence analysis as a CXC chemokine co-produced with IL-8 by osteosarcoma cells. Furthermore, the complete coding domain of human GCP-2 was disclosed by means of RT-PCR. Similarly, mouse GCP-2 was isolated from fibroblastoid and epithelial cells and completely identified by sequence analysis. Human and mouse GCP-2 share 61% identical amino acids. Both chemokines occur as multiple NH2-terminally truncated forms. The shorter forms of mouse, but not those of human, GCP-2 showed a higher neutrophil chemotactic potency and gelatinase B releasing capacity. Mouse GCP-2 was a more potent neutrophil activator than human GCP-2, natural mouse KC, and MIP-2. Human GCP-2 was not chemotactic for monocytes, lymphocytes, or eosinophils. Quantitative studies of mRNA expression in diploid fibroblasts revealed GCP-2 induction by IL-1beta. Human GCP-2 induced [Ca2+]i increase in neutrophils, which was reciprocally desensitized by IL-8, GROalpha, and ENA-78. Human GCP-2 induced [Ca2+]i increases and chemotactic responses in both CXCR1- and CXCR2-transfected cells. Finally, GCP-2 provoked neutrophil accumulation and plasma extravasation in rabbit skin. In humans, GCP-2 complements the activity of IL-8 as neutrophil chemoattractant and activator but it constitutes a major neutrophil chemokine in the mouse. GCP-2 induces neutrophil chemotaxis and activation but it might also contribute to detrimental tissue damage in sepsis, acute respiratory distress syndrome, acute hypersensitivity reactions, and autoimmune diseases. It might also influence the invasive capacity of GCP-2-secreting tumor cells.
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PMID:Granulocyte chemotactic protein-2 and related CXC chemokines: from gene regulation to receptor usage. 936 9

Cardiopulmonary bypass (CPB) is associated with an inflammatory response, mainly caused by the trauma of surgery, contact of blood with the artificial surface of the circuit, and reperfusion injury, resulting in increased capillary permeability, respiratory distress, low cardiac output, and multiorgan failure. The inflammatory reaction includes an activation of the humoral and cellular immune system with enhanced release of cytokines. The present study focused on the effect of CPB on the time course of pro- and anti-inflammatory cytokines. In 20 patients undergoing coronary artery bypass grafting, the plasma concentration of interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-8, and IL-10 was investigated pre-, intra-, and postoperatively by enzyme-linked immunosorbent assay technique. With the exception of IFN-gamma, all the other cytokines could be detected in the patients plasma. However, neither TNF-alpha nor IL-1 beta and IL-2 revealed significant changes in concentration during the investigated time period. In contrast, IL-6 and IL-8 levels peaked early postoperatively, reaching median concentrations of 430 pg/ml (221 pg per ml/558 pg per ml; lower/upper quartiles, respectively) and approximately 12 pg/ml (0/17 pg/ml; lower/upper quartiles, respectively). IL-4 and IL-10, respectively, revealed maximal concentrations of approximately 2 pg/ml (0/39 pg/ml; lower/upper quartiles, respectively) and 208 pg/ml (76 pg per ml/380 pg per ml; lower/upper quartiles, respectively) immediately after protamine administration, preceding the maximal concentration of IL-6. The degree of the observed modulation of cytokine patterns during and after CPB seemed to be patient-dependent, since large interindividual variations in cytokine levels were observed, not only preoperatively, but especially during and following CPB. However, IL-6 and IL-10 showed the least interindividual variations, suggesting that these cytokines may give reliable information regarding modulation of the immune response following CPB and its consequences for the patient's outcome.
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PMID:Interindividual variations in cytokine levels following cardiopulmonary bypass. 949 62

The first fatal case caused by the new genome type 7i is described in an 8-month-old boy requiring long-term respiratory support who developed Reye's syndrome, acute respiratory distress, and bronchiolitis obliterans with fatal evolution. Adenovirus was detected in nasopharyngeal secretions and was persistently positive during hospitalization. IgM and IgG adenovirus antibody titers measured in serum by enzyme-linked immunoassay (EIA) were 1:32 and 1:800, respectively. Serum interleukins (IL) and interferons (IFN) measured by EIA were as follows: IL-2, 110 pg/ml; IL-6, 300 pg/ml; IL-8, 7,000 pg/ml; TNF-alpha, 35 pg/ml, IL-1 and IL-4 undetectable, IFN-alpha 2,200 pg/ml, and IFN-gamma 700 pg/ml. Virologic studies showed that adenovirus isolated belonged to subgenus B, and digestion of viral DNA with Bam HI, Sma I, Bgl II, and Hind III identified the isolate as belonging to genome type 7i. Autopsy showed bronchiolitis obliterans with diffuse alveolar damage and perivenular fatty degeneration with polymorphonuclear infiltrates in the periportal spaces. The difficulty in obtaining adequate oxygenation with minimization of iatrogenic oxygen injury is discussed.
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PMID:Fatal adenovirus infection associated with new genome type. 951 74

Viridans streptococci are a heterogeneous group of Gram-positive bacteria that are normal inhabitants of the mouth, upper gastrointestinal tract and oropharynx. These organisms are typically thought of as of low virulence, classically as the cause of infective endocarditis, although recently they have been implicated in serious infections in other settings. In particular, viridans group streptococci have been described as responsible for the alpha-streptococcal shock syndrome in neutropenic patients. The mechanism by which viridans streptococci cause bacteraemia associated with adult respiratory distress syndrome (ARDS) in these patients has not been elucidated. Using enzyme-linked immunosorbent assays, we compared the ability of cell-free bacterial supernatants derived from commensal and clinical strains of viridans streptococci to induce the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-alpha), tumour necrosis factor beta (TNF-beta) and interleukin 8 (IL-8) from human peripheral blood mononuclear cells (PBMC) in vitro. Supernatants of clinical isolates induced significantly more TNF-beta (P < 0.002) and IL-8 (P < 0.001) than did supernatants from commensal strains. The increased production of IL-8 by the clinical strains may be of importance in view of the role of IL-8 in the pathogenesis of the acute respiratory distress syndrome (ARDS), one of the principal clinical features of the alpha-streptococcal shock syndrome.
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PMID:Cytokine release and mitogenic activity in the viridans streptococcal shock syndrome. 961 75

Enzymes and other factors secreted by degranulating neutrophils (polymorphonuclear leukocytes, PMNs) mediate endothelial injury, thrombosis, and vascular remodeling. In bacteremia and sepsis syndrome and their consequent complications (including acute respiratory distress syndrome and systemic ischemia-reperfusion resulting from septic shock), neutrophil degranulation is an important mechanism of injury. In related studies, we found that human endothelial cells regulate neutrophil degranulation and that inflammatory cytokines induce synthesis of degranulating factors by human endothelial cells. Here we show that lipopolysaccharides (LPS) from gram-negative bacteria were the most potent agonists for release of degranulating activity by endothelial cells when compared to several cytokines and stimulatory factors. LPS also induced the release of degranulating signals for PMNs from a human endothelial cell line, EA.hy 926. Interleukin 8 (IL-8) is synthesized by endothelial and EA.hy 926 cells in response to LPS and induces neutrophil degranulation. However, complementary strategies using receptor desensitization, translation of messenger RNA by Xenopus laevis oocytes, and purification and analysis of factors from conditioned supernatants demonstrated that degranulating factors distinct from IL8 are generated in response to LPS. The characteristics of a partially purified degranulating factor isolated from conditioned supernatants distinguished it from known chemokines and other factors that induce PMN degranulation and are generated by endothelial cells in response to LPS. Thus, cultured human endothelial cells and endothelial cell lines synthesize several unique signaling molecules that can trigger neutrophil granular secretion. If produced in vivo in response to LPS or other pathologic agonists, these degranulating signals may activate PMNs in combination or in sequence, initiating or propagating vascular damage.
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PMID:Bacterial lipopolysaccharide induces endothelial cells to synthesize a degranulating factor for neutrophils. 961 46

Staphylococcal enterotoxin A (SEA), a superantigen produced by some strains of Staphylococcus aureus, causes a variety of clinical manifestations ranging from food poisoning to shock. S. aureus can also be associated with the development of acute respiratory distress syndrome, and SEA has been shown to cause an inflammatory reaction in the lung. Therefore, we examined possible interactions between SEA, PBMCs, polymorphonuclear cells (PMNs), and normal human lung microvascular endothelial cells (HMVEC-L), as well as the role of these interactions on the secretion of IL-8. Injury to HMVEC-L, as measured by the release of 51Cr, increased significantly when HMVEC-L were incubated with SEA and PBMCs. IL-8 was secreted by both PBMCs and HMVEC-L. The accumulation of IL-8 in the culture medium of HMVEC-L was increased by SEA in a dose-dependent manner and was directly related to the number of PBMCs present. Although neither anti-human IL-8 nor IL-1 mAb inhibited HMVEC-L cytotoxicity, anti-human TNF-alpha mAb inhibited both the cytotoxicity and IL-8 accumulation completely. When HMVEC-L were incubated with supernatants from SEA-treated PBMCs, HMVEC-L cytotoxicity was comparable with HMVEC-L incubated with SEA and PBMCs at the same time. Although high concentrations of purified PMNs induced HMVEC-L lysis in a dose-dependent manner, the effect of PMNs was not changed in the presence of SEA. These findings suggest that TNF-alpha secreted by SEA-stimulated PBMCs plays a leading role in HMVEC-L injury.
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PMID:Staphylococcal enterotoxin A-induced injury of human lung endothelial cells and IL-8 accumulation are mediated by TNF-alpha. 982 May 42


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