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)

We reviewed the literature related to the effects of high-dose zinc in arteriosclerosis-induced angina pectoris. Lipid peroxidation and LDL oxidation are believed to be critical for arteriosclerosis, and consequently angina pectoris. Administration of biologically available zinc was a beneficial treatment in a significant percentage of patients with severely symptomatic, inoperable atherosclerotic disease. In these patients, there was no difference in zinc concentration between patients with and without atherosclerosis in whole blood, erythocytes or hair, but there was a major difference between normal aorta and diseased aortas (40.6 ppm zinc in normal aorta vs. 23.2 ppm zinc in atherosclerotic aorta, 40.6 ppm zinc in normal aorta vs. 19.4 ppm zinc in atherosclerotic aneurysm aorta, and no difference between normal and aneurysm aorta), although copper was low in aneurysm aorta. Medication with high-dose zinc sulfate to raise zinc serum concentrations from 95 to 177 microg/dl resulted in objective improvement in 12 of 16 of these patients, including a patient that also had Raynaud's disease. Long term environmental exposure to zinc resulted in a 40% reduction in the incidence of angina of effort compared to people not exposed to environmental zinc (P<0.01) and a 40% reduction in the incidence of probable ischemia in exercise (P<0.001). Lead had no effect while cadmium exposure resulted in more than tripling the incidence of angina of effort (P<0.001). The antioxidative action of zinc prevents oxidation of LDL cholesterol and consequently stops the main mechanism of atherogenesis. Zinc blocks calcium and its several actions on atherogenesis. Increased amounts of cytotoxic cytokines such as TNF-alpha, IL-beta and IL-8, often produced in the elderly, are blocked by high-dose zinc. We hypothesize that higher serum concentrations of LDL cholesterol resulting from administration of 300 mg of zinc per day is caused by a release of low density cholesterol from cardiovascular tissues, beneficially flushing it into the serum where it is readily observed, thus decreasing arteriosclerosis, increasing circulation, terminating angina pectoris and restoring more youthful cardiac function. Although prevention of cholesterol-induced arteriosclerosis by zinc is predicted from findings related to oxidative stress and lipid peroxidation, removal of LDL might be attributable to action of ionic zinc on ICAM inhibition. In stark contrast to current practice, high-dose zinc should be considered as basic in the strategy of prophylaxis and therapy of the atherosclerosis process to terminate angina pectoris and restore youthful cardiac function.
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PMID:High-dose zinc to terminate angina pectoris: a review and hypothesis for action by ICAM inhibition. 1608 66

Activated leukocytes are implicated in development of ischemia/reperfusion (I/R)-induced organ injuries. Phosphodiesterase 3 inhibitors have anti-inflammatory effects by preventing cyclic adenosine monophosphate (cAMP) degradation. We examined the effects of olprinone, a specific phosphodiesterase 3 inhibitor, on I/R-induced acute renal injury model in rats. Forty-five minute renal I/R was induced in uni-nephrectomized rats. Rats were divided into a vehicle group, an olprinone group, and a dibutyril (DB) cAMP group. Olprinone (0.2 microg/kg/minute) infusion began 30 min after reperfusion and continued for 3 h. DBcAMP (5 mg/kg), a stable analog of cAMP, was intraperitoneally administered 5 min after reperfusion to clarify the effect of cAMP in our model. Olprinone reduced the I/R-induced increases in serum levels of blood urea nitrogen and creatinine, and improved histological changes, including acute tubular necrosis in the outer medulla. Hemodynamic status was not affected by olprinone. I/R-induced a decrease in renal tissue blood flow, an increase in renal vascular permeability, and an enhancement of leukocyte activation, reflected by renal tissue levels of myeloperoxidase activity, and the tissue levels of cytokine-induced neutrophil chemoattractant (an equivalent of human interleukin 8) and tumor necrosis factor-alpha were all significantly decreased by olprinone. Olprinone also increased the renal tissue and plasma levels of cAMP in rats subjected to renal I/R. DBcAMP showed similar effects. Our results indicated that olprinone reduced the I/R-induced acute renal injury, probably by inhibiting leukocyte activation. The effects of olprinone could be explained through its action on cAMP levels.
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PMID:Olprinone reduces ischemia/reperfusion-induced acute renal injury in rats through enhancement of cAMP. 1613 69

Sepsis causes more than with 215,000 deaths per year in the United States alone. Death can be caused by multiple system organ failure, with the lung, in the form of the acute respiratory distress syndrome (ARDS), often being the first organ to fail. We developed a chronic porcine model of septic shock and ARDS and hypothesized that blocking the proteases neutrophil elastase (NE) and matrix metalloproteinases (MMP-2 and MMP-9) with the modified tetracycline, COL-3, would significantly improve morbidity in this model. Pigs were anesthetized and instrumented for hemodynamic monitoring and were then randomized to one of three groups: control (n = 3), laparotomy only; superior mesenteric artery occlusion (SMA) + fecal blood clot (FC; n = 7), with intraperitoneal placement of a FC; and SMA + FC + COL (n = 5), ingestion of COL-3 12 h before injury. Animals emerged from anesthesia and were monitored and treated with fluids and antibiotics in an animal intensive care unit continuously for 48 h. Serum and bronchoalveolar lavage fluid (BALF) were sampled and bacterial cultures, MMP-2, MMP-9, NE, and multiple cytokine concentrations were measured. Pigs were reanesthetized and placed on a ventilator when significant lung impairment occurred (PaO2/FiO2 < 250). At necropsy, lung water and histology were assessed. All animals in the SMA + FC group developed septic shock evidenced by a significant fall in arterial blood pressure that was not responsive to fluids. Lung injury typical of ARDS (i.e., a fall in lung compliance and PaO2/FiO2 ratio and a significant increase in lung water) developed in this group. Additionally, there was a significant increase in plasma IL-1 and IL-6 and in BALF IL-6, IL-8, IL-10, NE, and protein concentration in the SMA + FC group. COL-3 treatment prevented septic shock and ARDS and significantly decreased cytokine levels in plasma and BALF. COL-3 treatment also significantly reduced NE activity (P < 0.05) and reduced MMP-2 and MMP-9 activity in BALF by 64% and 34%, respectively, compared with the SMA + FC group. We conclude that prophylactic COL-3 prevented the development of ARDS and unexpectedly also prevented septic shock in a chronic insidious onset animal model of sepsis-induced ARDS. The mechanism of this protection is unclear, as COL-3 inhibited numerous inflammatory mediators. Nevertheless, COL-3 significantly reduced the morbidity in a clinically applicable animal model, demonstrating the possibility that COL-3 may be useful in reducing the morbidity associated with sepsis and ischemia/reperfusion injury in patients.
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PMID:Chemically modified tetracycline prevents the development of septic shock and acute respiratory distress syndrome in a clinically applicable porcine model. 1620 20

Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis, recognized as an inflammatory disease of the vessel wall, probably accelerated by diabetes mellitus (DM). Elevated interleukin (IL)-6 levels have been associated with increased cardiovascular morbidity and a common polymorphism has been identified in the promoter region of the IL-6 gene. The aim of this prospective study was to investigate inflammatory mediators in PAD patients (+/- DM) and to investigate a possible relationship to the IL-6 gene polymorphism. Five groups of patients (DM, intermittent claudication +/- DM, critical limb ischemia (CLI) +/- DM) and a control group of 20 individuals each were included. Hemoglobin, high sensitive C-reactive protein (hsCRP), creatinine, blood lipids, white blood cells (WBC); CD11b/CD18; vascular cell adhesion molecule (sVCAM-1), intercellular adhesion molecule (sICAM-1), sE-selectin, sP-selectin; IL-6, IL-8, tumour necrosis factor (TNF)alpha, sTNFalpha-R1 and sTNFalpha-R2 were analysed. The IL-6 gene polymorphism was determined in all groups and also compared with 200 healthy controls from a larger study of blood donors. In a multiple regression analysis, adjusted for gender, smoking and age, the effect of CLI was significantly (p < 0.05) associated with elevated levels of the WBC count, hsCRP, proinflammatory cytokines (IL-6, TNFalpha-R1-2) and endothelial (sICAM, sVCAM) and WBC (CD11b gran) markers. The effect of less advanced PAD (intermittent claudication) was related to an increased concentration of sVCAM-1 and the number of monocytes and granulocytes. DM or leg ulcers were not significantly related to any of the markers. No significant difference in frequency of the various IL-6 genotypes was found between the groups or when compared with the group of 200 blood donors (p> 0.3). Activation of cytokines, endothelial cells and WBC was related to the Fontaine stage of PAD but not to the presence of DM or ulcers. No association was found between the polymorphism in the IL-6 promoter region and PAD.
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PMID:Inflammatory markers and IL-6 polymorphism in peripheral arterial disease with and without diabetes mellitus. 1623 72

The pathogenesis of skin scleroderma (LS) is still unknown. Disturbances of vessels system, connective tissue metabolism and humoral and cellular immunological response is observed. Antinuclear antibodies are detected in 30-80% of patients with different types of skin scleroderma. They are present more often in patients with disseminated lesions and linear type of LS compared to morphoea au plaque. In our own analysis 28.5% of patients had also antibodies directed against Borrelia burgdorferi. It is believed that the injury of endothelial cells and proliferation in medial part of small vessels - which both lead to chronic ischemia - are the earliest disturbances observed in histopathological examination of the skin taken from systemic as well as from skin scleroderma patients. During last few years, there were some interesting reports concerning functional changes of endothelial cells which led to disturbances in tension of vessels smooth muscles. Free radicals - in genetically predispose people--can also provoke scleroderma lesions through their injury action on endothelial cells and stimulation of fibroblasts. In morphoea, the process of fibrosis begins around vessels. Deposition of connective tissue matrix is observed, especially collagen type I and III. This stimulation of fibroblasts as well as accumulation of connective tissue matrix are secondary to some stimulatory factors. These are: PDF, bFGF, TGFbeta and some cytokines. In morphoea patients serum levels of IL-1, IL-2, IL-4, IL-6 and IL-8 were elevated. In literature, levels and production of collagenases were decreased, although more authors say that tissue inhibitors of metalloproteinases are the main factor in fibrosis. The analysis of data tends to suspicion that enormous fibrosis observed in different types of scleroderma can be the result of increased production of collagen and other components of connective tissue as well as their incomplete degradation. Presented clinical and laboratory data show how many different factors influence etiopathogenesis of morphoea.
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PMID:[Pathogenesis of skin scleroderma--literature review]. 1633 38

In the adult, new blood vessel formation can occur either through angiogenesis from pre-existing mature endothelium or vasculogenesis mediated by bone marrow-derived endothelial precursors. We recently isolated endothelial progenitor cells, or angioblasts, in human adult bone marrow which have selective migratory properties for ischemic tissues, including myocardium, to where they home and induce vasculogenesis. Here we show that myocardial production of the IL-8/Gro-alpha CXC chemokine family is significantly increased after acute ischemia, and that this provides a chemoattractant gradient for bone marrow-derived endothelial progenitors, or angioblasts. This chemokine-mediated homing of bone marrow angioblasts to the ischemic heart regulates their ability to induce myocardial neovascularization, protection against cardiomyocyte apoptosis, and functional cardiac recovery. Together, our results indicate that CXC chemokines play a central role in regulating vasculogenesis in the adult, and suggest that manipulation of interactions between chemokines and their receptors on autologous human bone marrow-derived angioblasts could augment neovascularization of ischemic myocardial tissue.
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PMID:Myocardial homing and neovascularization by human bone marrow angioblasts is regulated by IL-8/Gro CXC chemokines. 1651 15

The potential therapeutic benefits from human umbilical cord blood (HUCB) cells for the treatment of injuries, diseases, and neurodegeneration are becoming increasingly recognized. The transplantation or infusion of cord blood cells in various animal models, such as ischemia/stroke, traumatic brain injury, myocardial infarction, Parkinson's disease, and amyotropic lateral sclerosis, has resulted in amelioration of behavioral deficits, and with some diseases, a prolonged lifespan decreased neuropathology. Previously, we reported the migration of HUCB cells to ischemic brain supernatant (tissue extracts) is time-dependent, and the expression of specific chemokines responds to this migration pattern. The mechanism(s) responsible for these effects are unknown. The expression of cytokines and chemokines produced by HUCB cells (under various culturing conditions) was investigated in this study. IL-8, MCP-1, and IL-1alpha were consistently expressed by the HUCB mononuclear cells regardless of the culture condition. These results provide insights to factors that may be partially responsible for the functional improvements seen in the animal models of injury investigating the therapeutic use of HUCB cells.
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PMID:Cytokines produced by cultured human umbilical cord blood (HUCB) cells: implications for brain repair. 1673 Mar 51

Increased Troponin I levels and pro-inflammatory cytokines have been reported in most patients undergoing cardiac surgery, ascribed to the type and extent of surgery, reperfusion injury, and the method of myocardial protection. We investigated their levels in patients undergoing on-pump (CCAB) or off-pump (OPCAB) coronary artery bypass surgery and whether these correlated with the extent of myocardial injury. One hundred twenty patients were prospectively randomized to undergo OPCAB (n = 60) or CCAB (n = 60). Hemodynamic and respiratory data, as well as serum CK-MB mass fraction, Troponin I, and interleukin (IL)-6, IL-8, and IL-10 levels, were collected perioperatively. Demographic, hemodynamic, and respiratory parameters were similar between the two groups. Troponin I was significantly lower in the OPCAB than in the CCAB group, either at the end of ischemia, end of surgery, 6-hour and 24-hour postoperatively (4 +/- 3, 5 +/- 3, 7 +/- 5, and 8 +/- 3 microg/L, vs. 19 +/- 18, 27 +/- 19, 28 +/- 13.5, and 33 +/- 8.5 microg/L, respectively, p < 0.05). Serum cytokine levels in the OPCAB patients were lower compared to the CCAB group at the end of surgery (32 +/- 35, 25 +/- 30, and 40 +/- 30 pg/ml for IL-6, IL-8, and IL-10 vs. 230 +/- 30, 140 +/- 70, and 125 +/- 50 pg/ml, respectively, p < 0.05). Plasma IL-6 levels correlated with the Troponin I levels at the end of surgery in both groups (r = 0.45, p = 0.01). Thus, OPCAB surgery is associated with reduced levels of Troponin I and activation of cytokines, compared to those in the CCAB group. High levels of these factors could correlate with myocardial damage during coronary artery bypass surgery. This finding warrants further laboratory and clinical confirmation in the future.
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PMID:Higher levels of serum cytokines and myocardial tissue markers during on-pump versus off-pump coronary artery bypass surgery. 1684 20

This study has been conducted in an effort to establish metabolic and inflammatory responses of the myocardium during aortic valve surgery on the beating heart with CPB and continuous coronary sinus perfusion with normothermic blood. Twenty patients, divided into two groups, participated in this study. Conventional aortic valvular operations were performed on first 10 patients, while the second group, consisting of 10 patients as well, was subjected to the operations with CPB on the beating heart with continuously perfusion with blood through coronary sinus. There were total of 14 biological and 6 mechanical valves implanted in aortic position. In this study, cardiac markers and inflammatory mediators IL-8 and TNF, were measured preoperatively and postoperatively. Metabolic changes were documented based on the levels of CK-MB, troponin I, myoglobin and LDH. Inflammatory factors we measured through IL-8 and TNF. All measurements were taken in 6 hour intervals during the initial 48 hours following the operations. The patients of "the beating heart" group had significantly lower dose of markers and cytokines in comparison to those who had undergone the conventional valvular operation. The elimination of the adverse effects of global ischemia produced from reperfusion injury and the similarity to the physiological condition, suggests that the revival of the beating heart procedure is more reasonable. This procedure of valvular surgery on the beating heart can be one of the good surgical options for the high-risk valvular patients.
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PMID:Inflammatory and metabolic response of the myocardium during aortic valve surgery on the beating heart. 1687 16

Neutrophil infiltration is mainly mediated by ELR+ CXC chemokines and is regulated through interactions between various stimulants and cells, which are perhaps more complex than previously thought. In this review, I describe the current view of the roles of neutrophil-selective chemokines such as IL-8, MIP-2, and KC by choosing several in vivo models. I also illustrate how these three chemokines are induced and how they are involved in neutrophil infiltration. Finally, I introduce synthetic compounds with high efficacy in the prevention of ischemia reperfusion injury.
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PMID:Neutrophil infiltration and chemokines. 1707 56


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