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)

This review article integrates empirical findings from various scientific disciplines into a proposed psychoneuroimmunological (PNI) model of the acute coronary syndrome (ACS). Our starting point is an existing, mild, atherosclerotic plaque and a dysfunctional endothelium. The ACS is triggered by three stages. (1) Plaque instability: Pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha) and chemoattractants (MCP-1, IL-8) induce leukocyte chemoattraction to the endothelium, and together with other triggers such as the CD40L-CD40 co-stimulation system activate plaque monocytes (macrophages). The macrophages then produce matrix metalloproteinases that disintegrate extra-cellular plaque matrix, causing coronary plaque instability. Acute stress, hostility, depression and vital exhaustion (VE) have been associated with elevated pro-inflammatory cytokines and leukocyte levels and their recruitment. (2) Extra-plaque factors promoting rupture: Neuro-endocrinological factors (norepinephrine) and cytokines induce vasoconstriction and elevated blood pressure (BP), both provoking a vulnerable plaque to rupture. Hostility/anger and acute stress can lead to vasoconstriction and elevated BP via catecholamines. (3) Superimposed thrombosis at a ruptured site: Increases in coagulation factors and reductions in anticoagulation factors (e.g. protein C) induced by inflammatory factors enhance platelet aggregation, a key stage in thrombosis. Hostility, depression and VE have been positively correlated with platelet aggregation. Thrombosis can lead to severe coronary occlusion, clinically manifested as an ACS. Thus, PNI processes might, at least in part, contribute to the pathogenesis of the ACS. This chain of events may endure due to lack of neuroendocrine-to-immune negative feedback stemming from cortisol resistance. This model has implications for the use of psychological interventions in ACS patients.
Cardiovasc Res 2002 Oct
PMID:Molecular and cellular interface between behavior and acute coronary syndromes. 1223 62

The systemic inflammatory response to cardiopulmonary bypass (CPB) may contribute to the development of postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits have been developed to reduce the risk of such complications. We compared the biocompatibility of these circuits. Twelve patients scheduled to undergo elective coronary artery bypass grafting (CABG) with CPB were assigned to CPB with a PMEA-coated circuit (PMEA-coated group, n=6) or a heparin-coated circuit (heparin-coated group, n=6). The plasma concentrations of the following inflammatory markers were measured before CPB and just after, 4 hours after, and 24 hours after the termination of CPB: cytokines (interleukin [IL]-6, IL-8, IL-10), complement factor (C3a), polymorphonuclear elastase (PMNE), and coagulofibrinolytic factors (thrombin-antithrombin III complex [TAT], D-dimer). Postoperative clinical response was evaluated on the basis of respiratory index, blood loss, and the postoperative and preoperative body-weight percent ratio. There were no significant differences between the groups in the plasma concentrations of IL-6, IL-10, C3a, PMNE, TAT, or D-dimer. Plasma IL-8 concentrations were below the assay detection limits at all time points in both groups. Clinical variables did not differ significantly between the groups. In conclusion, PMEA-coated CPB circuits are as biocompatible as heparin-coated CPB circuits and prevent postoperative organ dysfunction in patients undergoing elective CABG with CPB.
Ann Thorac Cardiovasc Surg 2003 Feb
PMID:Biocompatibility of poly2methoxyethylacrylate coating for cardiopulmonary bypass. 1266 26

The authors studied the relationship between cardiac cytokine release and pump function and whether low-dose application of sodium nitroprusside (SNP) improves cardiac performance during coronary artery bypass graft (CABG) creation. Cardiac reperfusion and application of nitric oxide have an influence on cytokine release. However, the functional consequences are unclear. Patients with CABGs (n = 30) with severely compromised left ventricular ejection fraction (<40%) were treated with either SNP (0.5 microg/kg/min) or placebo for the first 60 minutes of reperfusion after cardiac arrest. Interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-alpha were determined in blood samples from the radial artery and coronary sinus during reperfusion (5, 35, and 75 minutes). Hemodynamic measurements were performed before and after cardiopulmonary bypass and at the end of surgery. In all patients, the cardiac index at the end of surgery correlated negatively with levels of TNF-alpha at 5 minutes (r = 0.398; P < 0.05), IL-8 at 35 minutes (r = 0.394; P < 0.05), and IL-6 at 75 minutes of reperfusion (r = 0.421; P < 0.025). Sodium nitroprusside improved the cardiac index immediately after reperfusion (4.4 L/min/m2 +/- 0.3 vs. 3.7 L/min/m2 +/- 0.1; P = 0.014) and at the end of surgery (3.8 L/min/m2 +/- 0.3 vs. 3.0 L/min/m2 +/- 0.2; P = 0.023). The negative correlation between cardiac index and transcardiac cytokines suggests that reducing cardiac inflammatory reaction improves postischemic cardiac function. This was achieved by treating CABG patients with the nitric oxide donor SNP at a dosage without vasodilatory action.
J Cardiovasc Pharmacol 2003 Sep
PMID:Beneficial effect of sodium nitroprusside after coronary artery bypass surgery: pump function correlates inversely with cardiac release of proinflammatory cytokines. 1296 Jun 82

Recent studies have evaluated the cytokine network involved in the local immune response to tumors. In addition to infiltrating inflammatory cells, tumors also produce cytokines and growth factors that may alter tumor growth and tumor immunogenicity. Ninety-one samples of NSCLC were used in this study. We measured the expression of VEGF, TNF-alpha, TGF-beta, IL-6, IL-8, IL-12, INF-gamma, and MCP-1 in NSCLC tissues, by ELISA. The expression of IL-6 and IL-8 were significantly higher in squamous cell carcinoma than in adenocarcinoma (p=0.016 and p<0.001, respectively). The expression of TGF-beta, MCP-1 and IL-8 were significantly higher in pulmonary metastasis positive than negative cases (p=0.002, p=0.001, and p=0.008, respectively). In multivariate logistic regression analysis, the expression of TGF-beta was an independent risk factor for the occurrence of pulmonary metastasis (p=0.008, 95% CI=1.002-1.011). We confirmed that tumor infiltrating stromal cells were major sources of TGF-beta by immunohistochemical analysis. The expression of VEGF and IL-8 were significantly higher in cases with central necrosis (p=0.006 and p=0.011, respectively). We speculated that TGF-beta expression in tumor infiltrating stromal cells may regulate the occurrence of spontaneous pulmonary metastasis in NSCLC. (Ann Thorac Cardiovasc Surg 2003; 9: 295-300)
Ann Thorac Cardiovasc Surg 2003 Oct
PMID:Significance of expression of TGF-beta in pulmonary metastasis in non-small cell lung cancer tissues. 1467 25

Interleukin-8 (IL-8), a member of CXC chemokine family, has been found to play an important role in the pathogenesis of atherosclerosis. Tumor necrosis factor-alpha (TNF-alpha) is involved in the development and progression of atherosclerosis as well. In this study, we investigated whether and how azelnidipine, a newly developed long-acting calcium antagonist, could inhibit TNF-alpha-induced IL-8 expression in human umbilical vein endothelial cells (HUVEC). TNF-alpha significantly increased intracellular reactive oxygen species (ROS) generation in HUVEC, which was completely blocked by azelnidipine or apocynin, an inhibitor of NADPH oxidase. Azelnidipine also completely prevented TNF-alpha-induced increase in NADPH oxidase activity in HUVEC. Further, azelnidipine was found to significantly inhibit activator protein-1 (AP-1) promoter activity and IL-8 expression in TNF-alpha-exposed HUVEC. An inhibitor of AP-1, curcumin, or an anti-oxidant, N-acetylcysteine, also inhibited the TNF-alpha-induced IL-8 expression in HUVEC. These results demonstrated that azelnidipine inhibited TNF-alpha-induced IL-8 expression in HUVEC by blocking NADPH oxidase-mediated ROS generation and subsequent AP-1 activation. Our present study suggests that azelnidipine may play a protective role in the development and progression of atherosclerosis through its anti-oxidative properties.
J Cardiovasc Pharmacol 2004 May
PMID:Azelnidipine, a newly developed long-acting calcium antagonist, inhibits tumor necrosis factor-alpha-induced interleukin-8 expression in endothelial cells through its anti-oxidative properties. 1507 61

Migration of leukocytes into the vasculature-which involves the concerted effort of many molecules, including chemokines-is a requisite step for atherogenesis. The three chemokines that have been implicated most strongly in atherogenesis are monocyte chemoattractant protein 1 (MCP-1), interleukin 8 (IL-8)/growth-regulated oncogene alpha (Gro-alpha), and fractalkine. Although all three chemokines appear to impact atherogenesis by attenuating monocyte/macrophage accumulation in the lesion, the precise mechanism of action of each of the chemokines, as well as their interactive role in atherosclerosis, have not been elucidated. This review focuses on the latest findings that describe the individual roles of MCP-1, IL-8/Gro-alpha, and fractalkine on macrophage recruitment in atherosclerosis. Furthermore, based on present knowledge of the participation of these three chemokines and their receptors in monocyte/macrophage recruitment, a possible interactive role of these chemokines in atherogenesis is explored.
Trends Cardiovasc Med 2004 May
PMID:Modulation of atherogenesis by chemokines. 1517 67

Chemokine expression is markedly upregulated in healing myocardial infarcts and may play an important role in regulating leukocyte infiltration and activity and in modulating infarct angiogenesis as well as fibrous tissue deposition. The CC chemokine monocyte chemoattractant protein-1/CCL2 has important effects in infarct healing. Monocyte chemoattractant protein-1 -/- mice exhibit reduced macrophage infiltration and activation, suppressed cytokine synthesis, delayed phagocytotic removal of dead cardiomyocytes, diminished myofibroblast accumulation, and decreased ventricular remodeling after myocardial infarction. Monocyte chemoattractant protein-1 may also play an important role in the development of interstitial fibrosis in ischemic noninfarctive cardiomyopathy. CXC chemokines are also induced in healing infarcts. Interleukin-8/CXCL8 may mediate neutrophil recruitment and activation and may promote neovessel formation, whereas induction of the angiostatic and antifibrotic chemokine interferon-gamma-inducible protein-10/CXCL10 may serve to prevent premature wound angiogenesis and fibrous tissue deposition in the infarct, until the injured myocardium has been cleared from dead cells and debris and a fibrin-rich provisional matrix is formed. Understanding of the role of chemokines in myocardial ischemia may result in novel strategies in the treatment of patients with ischemic heart disease.
Trends Cardiovasc Med 2005 Jul
PMID:Chemokines in myocardial ischemia. 1616 12

Cardiopulmonary bypass may cause acute lung injury and can seriously affect postoperative outcome, especially in younger patients. A synthesized neutrophil elastase inhibitor, sivelestat sodium, may be most effective when used during cardiopulmonary bypass. After anesthesia induction, sivelestat (2 mg/kg/h) was given to the SS group (n=7), and 0.9% saline solution to the placebo group (n=7). Piglets were placed on hypothermic cardiopulmonary bypass and subjected to myocardial ischemia (2 h) induced by cold crystalloid cardioplegia. At 24 h after surgery, PaO(2)/FiO(2) ratio and alveolar-arterial oxygen difference were significantly better in the SS group (379.1+/-93.9 mmHg and 250.5+/-89.3 mmHg) than the placebo group (232.4+/-105.3 mmHg, and 378.3+/-90.8 mmHg, P<0.05). Interleukin-8 level in the epithelial lining fluid was above the lowest standard in 6 out of 7 (4.5, 12.9, 24.6, 27.7, 37.7, and 159.8; mean=44.5+/-57.6 g/l) in the placebo group, and in 2 out of 7 (36.1 and 67.8 g/l) in the SS group (P<0.05). The median histological score of acute lung injury in the harvested lung was 3 (2-5) in the placebo group and 1 (1-5) in the SS group (P<0.05). Intraoperative administration of sivelestat effectively reduced neutrophil induction and activation in the lung and improved oxygenation after cardiopulmonary bypass in a piglet model.
Interact Cardiovasc Thorac Surg 2008 Oct
PMID:The effect of sivelestat sodium on post-cardiopulmonary bypass acute lung injury in a neonatal piglet model. 1859 53

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, is steroid therapy ever of benefit to patients in the intensive care unit going into septic shock? Using the reported search 1505 papers were identified. Fourteen papers represented the best evidence on the subject. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study comments and weaknesses were tabulated. Recent guidelines from the Surviving Sepsis Campaign recommend using stress doses of corticosteroids for septic shock regardless of adrenal function. All patients undergoing cardiothoracic surgery are at risk of developing septic shock. The 14 papers demonstrated that 28-day mortality is unaffected by hydrocortisone, however, the time to shock reversal is significantly reduced. Steroids reduced inflammatory mediators (IL-6, IL-8 and CRP) and neutrophil activation whilst maintaining neutrophil phagocytic functions. Haemodynamically, they increased systemic vascular resistance (SVR) and mean arterial pressure (MAP) and reduced heart rate (HR) and glomerular permeability. We conclude that steroids have no effect on mortality but shorten time to shock reversal, therefore they have a limited capacity in septic shock patients. Their immunological and haemodynamic effects cannot be discounted and could benefit patients in severe septic shock with adrenal insufficiency.
Interact Cardiovasc Thorac Surg 2008 Oct
PMID:Is steroid therapy ever of benefit to patients in the intensive care unit going into septic shock. 1864 22

Extensive investigations have implicated cytokines such as tumour necrosis factor (TNF)- alpha and interleukin (IL)-1, and IL-6 as contributing to the pathology of ischemia-reperfusion (I/R) injury, since an increase in the production of those cytokines was clinically detected after myocardial infarction and cardiopulmonary bypass surgery. Current evidence indicates that these cytokines are autocrine contributors to myocardial dysfunction and cardiomyocyte necrosis in I/R injury, whereas, earlier evidence also suggest that cytokines have controversial roles in cardiovascular pathophysiology. Accordingly, it becomes vital to better define the mechanisms of action of cytokines as important steps towards the development of effective therapeutic strategies to combat their deleterious effects in ischemia-induced myocardial injury. Since TNF-alpha, TGF-beta1, IL-1, IL-6 and IL-8 have been frequently studied in cardiovascular diseases, especially in I/R heart disease, the purpose of this article is to review the cardiodepressant role of these cytokines and their release in I/R injury.
Cardiovasc Hematol Disord Drug Targets 2008 Sep
PMID:Status of cytokines in ischemia reperfusion induced heart injury. 1878 28


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