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)

To better understand the pathogenesis of acute respiratory distress syndrome (ARDS), we analyzed bronchoalveolar lavage fluid (BALF) from patients with ARDS (n = 89, survival rate = 56.2%), who were admitted to our intensive care units over the past 7 years. ARDS was diagnosed when the lung injury score proposed by Murray et al was greater than 2.5. The BALF had very high centrations of albumin, a marker of permeability edema, along with remarkably high neutrophil counts, percent neutrophils, neutrophil-elastase, and interleukin-8, markers of neutrophil-related lung injury. In addition, the level of IL-8 in BALF was higher in non-survivors than in survivors. Levels of thrombin-antithrombin complex fibrin degenerative product and soluble thrombomodulin (recently recognized as a natural anticoagulant combined with vascular endothelial cells) were very high in BALF from patients with ARDS. Moreover, the level of soluble thrombomodulin in BALF was higher in non-survivors than in survivors. There were significant relationships between these neutrophil-related markers and markers of abnormal coagulation. The results of the BALF analysis suggest that accumulation and activation of neutrophils can affect thrombomodulin on vascular endothelial cells, which can activate thrombin and cause the coagulopathy seen in ARDS.
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PMID:[Diagnosis of acute respiratory distress syndrome: analysis of bronchoalveolar lavage fluid]. 875 15

Fourteen patients undergoing cardiac or great vessel surgery using cardiopulmonary bypass (ECC) were divided into two groups. Group A of 7 patients received 2 x 10(6) units of aprotinin (apr) 15 min before ECC and 0.5 x 10(6) unit immediately after the ECC. Group B of 7 patients received 0.5 x 10(6) unit of aprotinin 15 min before ECC and 2 x 10(6) units immediately after the ECC. Several physiological parameters were measured two hours before ECC, immediately after the cessation of the ECC and 4 hours thereafter. No difference was noted in coagulation time, which remained within normal range, and postoperative hemorrhage between the groups after ECC. Although thrombomodulin, ELAM-1 and ICAM-1 tended to decrease slightly in the two groups immediately after ECC, recovery of the thrombomodulin was much more rapid in the A group than in the B group. On the other hand, blood endothelin level and von Willebrand factor activity were elevated progressively after the ECC. Blood granulocyte-elastase activity and IL-8 increased markedly immediately after the ECC and then tended to decrease. These data indicate that no marked damage would be caused on the endothelial cells during ECC which was carried out using a relatively small dose of apr. However, the protective effect of apr remained to be clarified in the future.
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PMID:[Effect of aprotinin on endothelial cell functions during cardiopulmonary bypass]. 881 86

By extrapolation from the responses of cultured human umbilical vein endothelial cells (EC) and bovine aortic EC to short-term cytokine stimulation, EC activation is postulated as a likely component of the host response in acute allograft rejection and cardiac transplant-associated accelerated arteriosclerosis. To investigate the extent to which EC activation occurs in vivo in humans and to identify potential targets for therapeutic interventions, we compared the phenotypic characteristics of vascular EC as seen during clinicopathologically significant vs non-significant acute cardiac allograft rejection. We used monoclonal and monospecific polyclonal antibodies to coagulation molecules [tissue factor, thrombomodulin (TM), antithrombin III (AT-III), fibrinogen/fibrin, cross-linked fibrin and von Willebrand factor (vWF)], adhesion molecules (P-selectin, ICAM-1) and major histocompatibility complex (MHC) class I and II molecules. In addition we sought evidence of local cytokine production (IL-1, IL-2R, IL-4, IL-6, IL-7, IL-8, TNF-alpha, PDGF-AA, PDGF-BB), which might mediate alterations in expression of these proteins. We found that in clinically significant grades of cardiac allograft rejection requiring increased immunosuppression, in contrast to lesser grades of rejection not requiring clinical intervention, there was increased microvascular EC activation and differential expression of cytokines. EC changes associated with more extensive cardiac allograft rejection requiring treatment included: (i) disruption of the normal anticoagulant state with downregulation of TM and AT-III, upregulation of tissue factor and vWF expression, and associated extensive fibrin deposition; (ii) upregulation of MHC class I antigens, which are potential targets for host cytotoxic T lymphocytes; (iii) increased expression of the leucocyte adhesion molecules P-selectin and ICAM-1; (iv) expression of the pro-inflammatory cytokines IL-1 beta and TNF-alpha; and (v) increased expression of PDGF-AA and BB, which are known to promote migration and proliferation of intimal cells, and hence may contribute to development of transplant-associated atherosclerosis. Collectively these findings suggest that immune events resulting in EC surface changes and/or production of key cytokines play a role in the pathogenesis of acute transplant rejection and may contribute to the long-term complication of accelerated arteriosclerosis in allograft coronary arteries.
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PMID:Endothelial activation and cytokine expression in human acute cardiac allograft rejection. 953 4

Cold preservation/reperfusion leads to sinusoidal endothelial cell (SEC) activation and damage in nearly every liver transplantation; the extent of these changes influences early graft function. Upon reperfusion, activated SEC show increased expression of adhesion molecules, including von Willebrand factor (vWF) which is released into the circulation. This study was designed to evaluate the levels of vWF measured in the caval effluent and correlate these findings with known markers of SEC damage and early graft function. Data were obtained from 35 patients undergoing orthotopic liver transplantation (LTx). Two samples were taken from each patient for measurement of vWF: a) from the portal vein immediately prior to reperfusion; and b) from the first 50 ml of the caval effluent. Commercial assays were used to measure vWF, as well as hyaluronic acid (HA), thrombomodulin (TM), IL-1 beta, IL-6, IL-8 and TNF-alpha. Patients were divided into two groups based on early graft function. Poor early graft function (PEGF) was defined as a peak aspartate transaminase (AST) or alanine transaminase (ALT) level > 2500 U/L during the first three postoperative days (POD) and a prothrombin time (PT) > 16 s on POD 2 (n = 8). The remaining 27 patients had good early graft function (GEGF). In patients with GEGF, vWF levels dropped significantly between the two time points. This change was not observed in those with PEGF. A positive linear correlation was observed in the PEGF group between vWF and HA and IL-6. The different pattern of change in vWF between the two groups, as well as the positive correlation between HA, IL-6 and vWF in PEGF, suggest that vWF may be a useful marker of early graft function.
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PMID:Correlation between von Willebrand factor levels and early graft function in clinical liver transplantation. 1008 31

We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome (SIRS) and 13 healthy volunteers serving as controls. Plasma levels of AM in SIRS (burns: 20.5 +/- 3. 2 fmol/ml [mean +/- SEM]; pancreatitis: 13.8 +/- 3.8 fmol/ml; trauma: 14.9 +/- 2.5 fmol/ml; traumatic shock: 41.1 +/- 7.8 fmol/ml; severe sepsis: 59.9 +/- 11.2 fmol/ml; septic shock: 193.5 +/- 30.1 fmol/ml) were significantly increased over those of controls (5.1 +/- 0.2 fmol/ml). The patients with traumatic shock or septic shock especially had higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS, plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1, and thrombomodulin (TM) in patients with traumatic shock and septic shock. A significant correlation was observed between plasma AM and TNF-alpha levels in patients with septic shock, suggesting an important role for AM as well as of TNF-alpha in the pathophysiology of inflammation. Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE) II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as did plasma IL-6 levels in patients with traumatic shock. The plasma AM level might serve as a useful marker for evaluating the severity of disease and as an early predictor of subsequent organ failure and outcome in septic shock.
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PMID:Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome. 1039 Mar 90

We investigated the significance of platelet activation and platelet-derived microparticles (PMP) in 14 patients with systemic inflammatory response syndrome (SIRS) and hematological malignancies. In the phenotypic analysis of lymphocytes, there was a significant decrease of total and activated T cells after panipenem/betamipron (PAPM/BP) treatment (p<0.05). The percentages of helper/inducer T cells and suppressor/cytotoxic T cells were insignificantly decreased after PAPM/BP treatment. The number of natural killer (NK) cells of potent activity was significantly decreased after treatment (p<0.05). The levels of the cytokines interleukin (IL)-1beta, IL-6, and IL-8 in the patients were increased before treatment. IL-1beta concentrations were not changed after treatment. In contrast, the IL-6 and IL-8 levels were significantly decreased (p<0.05) after treatment, while tumor necrosis factor (TNF)-alpha and interferon gamma remained almost normal. We found an increase of soluble IL-2 receptor (sIL-2R) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in the patients before treatment. After treatment, the sIL-2R concentrations tended to be decreased and sVCAM-1 levels showed a significant decrease (p<0.01). In contrast, soluble thrombomodulin (sTM) level did not change. Regarding the platelet activation markers, CD62P, CD63, and PMP levels in the patients were increased before treatment. CD62P and CD63 tended to be decreased after treatment, whereas PMP levels were significantly reduced from 1,056+/-103 to 762+/-64/10(4) platelets (p<0.05). Furthermore, CD62P, CD63, and PMP correlated with the levels of IL-6 and IL-8. These results suggest that activated platelets and PMP may be predictive markers in pre-disseminated intravascular coagulation and hypercytokine conditions related to SIRS.
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PMID:Relationship between platelet activation and cytokines in systemic inflammatory response syndrome patients with hematological malignancies. 1051 85

The effects of Duraflo II heparin coated cardiopulmonary bypass circuits, low-dose aprotinin, and steroids on the coagulation system, endothelial damage, and cytokine release were evaluated by comparing those treated with low-dose aprotinin and steroids. Twenty-four adult patients undergoing coronary artery bypass grafting, aortic valve replacement, or valve repair surgery were randomly assigned to 2 groups: either heparin-coated (Duraflo group, n = 12) or noncoated equipment (noncoated group, n = 12) groups. In the Duraflo group, the cardiopulmonary reservoir was also coated with heparin. There were no significant differences in age at the time of operation, aortic cross-clamp time, cardiopulmonary bypass time, and rectal temperature during cardiopulmonary bypass. Standard systemic heparinization was performed. Methylpredonisolone and low-dose aprotinin were given in both groups of patients. Serum XIIa factor, TAT, and IL-6 were significantly higher in the control group than in the Duraflo group during cardiopulmonary bypass (p < 0.01). Serum IL-8 was significantly higher in the control group than in the Duraflo group at 24 h after cardiopulmonary bypass (p < 0.05). No significant difference was found in serum thrombomodulin and TNF-alpha; both were within normal during the study period. These results indicate that the use of Duraflo II heparin coated equipment and a heparin-coated cardiopulmonary reservoir suppressed excess coagulation and inflammatory reaction induced by cardiopulmonary bypass.
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PMID:Effects of Duraflo II heparin-coated cardiopulmonary bypass circuits on the coagulation system, endothelial damage, and cytokine release in patients with cardiac operation employing aprotinin and steroids. 1061 29

The influence of the endothelial protein C receptor (EPCR) on the host response to Escherichia coli was studied. Animals were treated with 4 separate protocols for survival studies and analysis of physiologic and biochemical parameters: (1) monoclonal antibody (mAb) that blocks protein C/activated protein C binding to EPCR plus sublethal numbers of E coli (SLEC) (n = 4); (2) mAb to EPCR that does not block binding plus SLEC (n = 3); (3) SLEC alone (n = 4); and (4) blocking mAB alone (n = 1). Those animals receiving blocking mAb to EPCR plus sublethal E coli died 7 to 54 hours after challenge, whereas all animals treated with the other protocols were permanent survivors. Histopathologic studies of tissues from animals receiving blocking mAb plus SLEC removed at postmortem were compared with those animals receiving SLEC alone killed at T+24 hours. The animals receiving the blocking mAb exhibited consumption of fibrinogen, microvascular thrombosis with hemorrhage of both the adrenal and renal cortex, and an intense influx of neutrophils into the adrenal, renal, and hepatic microvasculature, whereas the tissues from animals receiving only sublethal E coli exhibited none of these abnormal histopathologic changes. Compared with the control animals, the animals receiving the blocking mAb exhibited significantly elevated serum glutamic pyruvic transaminase, anion gap, thrombin-antithrombin complex, IL-6, IL-8, and soluble thrombomodulin. The levels of circulating activated protein C varied too widely to allow a clear determination of whether the extent of protein C activation was altered in vivo by blocking protein C binding to EPCR. We conclude that protein C/activated protein C binding to EPCR contributes to the negative regulation of the coagulopathic and inflammatory response to E coli and that EPCR provides an additional critical step in the host defense against E coli. (Blood. 2000;95:1680-1686)
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PMID:The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. 1068 24

The vascular endothelium influences not only the three classically interacting components of hemostasis: the vessel, the blood platelets and the clotting and fibrinolytic systems of plasma, but also the natural sequelae: inflammation and tissue repair. Two principal modes of endothelial behaviour may be differentiated, best defined as an anti- and a prothrombotic state. Under physiological conditions endothelium mediates vascular dilatation (formation of NO, PGI2, adenosine, hyperpolarizing factor), prevents platelet adhesion and activation (production of adenosine, NO and PGI2, removal of ADP), blocks thrombin formation (tissue factor pathway inhibitor, activation of protein C via thrombomodulin, activation of antithrombin III) and mitigates fibrin deposition (t- and scuplasminogen activator production). Adhesion and transmigration of inflammatory leukocytes are attenuated, e.g. by NO and IL-10, and oxygen radicals are efficiently scavenged (urate, NO, glutathione, SOD). When the endothelium is physically disrupted or functionally perturbed by postischemic reperfusion, acute and chronic inflammation, atherosclerosis, diabetes and chronic arterial hypertension, then completely opposing actions pertain. This prothrombotic, proinflammatory state is characterised by vaso-constriction, platelet and leukocyte activation and adhesion (externalization, expression and upregulation of von Willebrand factor, platelet activating factor, P-selectin, ICAM-1, IL-8, MCP-1, TNF alpha, etc.), promotion of thrombin formation, coagulation and fibrin deposition at the vascular wall (expression of tissue factor, PAI-1, phosphatidyl serine, etc.) and, in platelet-leukocyte coaggregates, additional inflammatory interactions via attachment of platelet CD40-ligand to endothelial, monocyte and B-cell CD40. Since thrombin formation and inflammatory stimulation set the stage for later tissue repair, complete abolition of such endothelial responses cannot be the goal of clinical interventions aimed at limiting procoagulatory, prothrombotic actions of a dysfunctional vascular endothelium.
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PMID:Endothelial function and hemostasis. 1079 71

Allogeneic bone marrow transplantation was performed in a 24-year-old woman with acute myelogenous leukemia in the first remission (FAB classification: M4). Graft-versus-host disease occurred from around day 150 after bone marrow transplantation. The levels of tumour necrosis factor-alpha, interleukin 12, and intercellular adhesion molecule-1 were elevated in the early stage of graft-versus-host disease, followed by elevation of interleukin 10 and interleukin 8. Her symptoms subsequently improved and all of these parameters became normal. The levels of thrombomodulin and plasminogen activator inhibitor type 1 showed changes that were in parallel with the clinical course. Interleukin 1beta, interleukin 6, interleukin 2, and interferon-gamma showed no changes throughout the course of her graft-versus-host disease. These findings suggested the possibility that release of inflammatory molecules occurred at the onset of graft-versus-host disease and caused vascular endothelial damage, which led to the exacerbation of her disease.
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PMID:Changes of cytokines during the course of graft-versus-host disease following bone marrow transplantation: a case report. 1093 Mar


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