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)

It was hypothesized that IL-8, a neutrophil chemotaxin, contributes to the influx of neutrophils into the pleural cavity of patients with pleural effusions. Pleural fluids were collected from 57 patients including 13 with effusions due to congestive heart failure, 28 with pleural involvement by carcinoma, 5 with empyema, 4 with parapneumonic effusions complicating bacterial pneumonia, 3 with hemothorax, 3 with tuberculosis, and 1 with rheumatoid arthritis. All exudate groups had significantly higher IL-8 concentrations than the CHF group (p < .001). In 18 of the exudate fluids, the concentrations of IL-8 was equal to or in excess of the optimal concentration of IL-8 which causes neutrophil chemotaxis in vitro. Between 20 and 90% of the chemotactic activity in the fluids was removed by absorbing the IL-8 with an IL-8 affinity column. These data showed that IL-8 is a major chemotaxin in the fluid. The percentage of neutrophils in the fluids was not correlated with the IL-8 concentration. Although TNF alpha, a potent stimulator of IL-8 production, is present in some pleural effusions, no correlation was found between the concentrations of IL-8 and TNF alpha in the fluids. The data suggest that IL-8 contributes to the neutrophil influx into the pleural space of patients with pleural exudates in conjunction with other chemoattractants. It is unlikely that TNF alpha is the sole stimulus for the IL-8 production in pleural disease states.
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PMID:Interleukin-8: an important neutrophil chemotaxin in some cases of exudative pleural effusions. 825 60

In pneumonia local phagocyte activation is crucial for clearing of pathogenic microorganisms. In this context alveolar macrophage interleukin-8 secretion, phagocyte oxidative response and concentrations of lavage proteins were quantified, including interleukin-8, in 31 patients with pneumonia, 13 age matched patients with peripheral lung consolidation and six healthy volunteers; these findings were related to the impairment of gas exchange and the bacterial load in the alveolar space. Increased interleukin-8 levels were found in bronchoalveolar lavage fluid (BALF) and in alveolar macrophage supernatants from patients with pneumonia (214 ng/10(5) AM +/- 121 vs 71 ng/10(5) AM +/- 35 and 66 ng/10(5) AM +/- 30, p < 0.05). Interleukin-8 release from alveolar macrophages correlated with the upregulated spontaneous luminol enhanced oxidative response of pulmonary phagocytes but not with the neutrophil count in BALF. In pneumonia patients a significant difference was found between patients with 10(4) or more colony forming units (CFU)/ml BALF of one pathogen and patients with less CFU or nonspecific microbiological results (261 ng/10(5) AM +/- 89 vs 179 ng/10(5) AM +/- 81 and 7.5 ng/ml BALF +/- 17 vs 0.44 ng/ml BALF +/- 1, p < 0.05). Further, a negative correlation between interleukin-8 release of alveolar macrophages and the arterial pO2 at the time of BALF could be demonstrated (r = -0.47, p < 0.05). The results demonstrate local cellular activation in community-acquired pneumonia, which is related to the bacterial load in the alveolar space and to impairment of gas exchange. This is consistent with the hypothesis that pulmonary phagocytes play a central role in the pathogenesis of bacterial pneumonia, contributing not only to bacterial clearing but also to local tissue damage.
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PMID:Role of interleukin-8 in community-acquired pneumonia: relation to microbial load and pulmonary function. 910 84

To evaluate whether concentrations of cytokines supposed to be involved in eosinophil recruitment and activation were elevated in cystic fibrosis (CF), we assessed interleukin-3 (IL-3), IL-5, IL-8, regulated on activation, normal T-cell expressed and secreted (RANTES); and granulocyte-macrophage colony stimulating factor (GM-CSF) in sputa from 32 patients with CF, eight patients with atopic bronchial asthma, and six patients with bacterial pneumonia. In addition, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) were measured as markers of eosinophil activation. In patients with CF, sputum levels of IL-8 were elevated (p < 0.01) as compared with asthmatic patients. Concentrations of IL-3, ECP, and EPX were not different in the two groups. However, IL-5 (p < 0.0001), RANTES (p < 0.003), and GM-CSF (p < 0.0001) were significantly lower in the CF group than in subjects with asthma. IL-5 was detected only in sputum samples from CF patients with Aspergillus sensitization. In patients with pneumonia, IL-8 levels only were increased. In CF sputum, ECP levels were significantly correlated with the levels of IL-8 (r = 0.626, p < 0.0001) and IL-3 (r = 0.642; p < 0.0001), whereas in asthmatic patients IL-5, IL-8, and RANTES concentrations were significantly related to ECP in sputum. These findings suggest that different cytokine profiles are responsible for eosinophil activation in patients with CF as compared with asthmatic patients. In CF, IL-8 and IL-3 appear to be responsible for increased degranulation of eosinophils.
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PMID:Cytokine concentrations in sputum from patients with cystic fibrosis and their relation to eosinophil activity. 911 85

Human immunodeficiency virus (HIV)-infected patients are at increased risk of contracting bacterial infections, mainly pneumonia. Despite this, little is known about immunopathogenic mechanisms in HIV-related bacterial pneumonia. This paper investigates the presence of the neutrophil chemotactic mediators, interleukin-8 (IL_8) and leukotriene B4 (LTB4), in bronchoalveolar lavage (BAL) fluid from 27 HIV-infected patients with bacterial pneumonia. Significantly elevated levels of IL-8 were found in BAL fluid of patients with bacterial pneumonia [529 pg ml-1 (296-1161 pg ml-1)] compared to matched patients with Pneumocystis carinii pneumonia (PCP) [59 pg ml-1 (42-254 pg ml-1)] and healthy controls [58 pg ml-1 (37-82 pg ml-1)]. Levels of LTB4 were not elevated during bacterial pneumonia when compared to PCP patients and healthy controls. Furthermore, a positive correlation was found between IL-8 levels in BAL fluid and relative BAL neutrophilia (r = 0.60, P = 0.001) in bacterial pneumonia. In conclusion, elevated IL-8 levels in BAL fluid were found in patients suffering from bacterial pneumonia, which may account for the influx of neutrophils to the lung, whereas LTB4 appears not to be an important chemotactic factor in this setting.
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PMID:Interleukin-8 and leukotriene B4 in bronchoalveolar lavage fluid from HIV-infected patients with bacterial pneumonia. 917 51

Sputum and serum from patients with active pulmonary tuberculosis (TB), healthy purified protein derivative-positive adults, and patients with bacterial pneumonia were collected to simultaneously assess local immunity in the lungs and peripheral blood. To determine whether cytokine profiles in sputum from TB patients and control subjects were a reflection of its cellular composition, cytospin slides were prepared in parallel and assessed for the presence of relative proportions of epithelial cells, neutrophils, macrophages, and T cells. Gamma interferon (IFN-gamma) in sputum from TB patients was markedly elevated over levels for both control groups. With anti-TB therapy, IFN-gamma levels in sputum from TB patients decreased rapidly and by week 4 of treatment were comparable to those in sputum from controls. Further, IFN-gamma levels in sputum closely followed mycobacterial clearance. Although detected at fourfold-lower levels, IFN-gamma immunoreactivities in serum followed kinetics in sputum. TNF-alpha, interleukin 8 (IL-8) and IL-6 also were readily detected in sputum from TB patients at baseline and responded to anti-TB therapy. In contrast to IFN-gamma, however, TNF-alpha and IL-8 levels also were elevated in sputum from pneumonia controls. These data indicate that sputum cytokines correlate with disease activity during active TB of the lung and may serve as potential early markers for sputum conversion and response to anti-TB therapy.
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PMID:Sputum cytokine levels in patients with pulmonary tuberculosis as early markers of mycobacterial clearance. 1209 79

The ELR(+) CXC chemokines are critical for protective neutrophil responses to most bacterial infections, but nevertheless can contribute importantly to the pathogenic effects of many inflammatory responses. We recently engineered a series of high affinity CXCL8/IL-8 antagonists, one of which, CXCL8((3-73))K11R/G31P, binds very strongly to neutrophils via the CXCR1 and CXCR2. Herein we show in competitive 125I-ligand binding assays that bovine CXCL8((3-73))K11R/G31P has an affinity for neutrophils that is 2-3 orders of magnitude higher than that of CXCL8/IL-8. Furthermore, when used at approximately 0.5 nM, CXCL8((3-73))K11R/G31P inhibited by 50% the chemotactic responses of neutrophils to 129 nM CXCL8/IL-8, but it also blocked chemotactic responses to the alternate ELR-CXC chemokines CXCL1/GRO alpha and CXCL5/ENA-78. Furthermore, CXCL8((3-73))K11R/G31P could inhibit by 93-97% the spectrum of neutrophil chemotactic activities present within wash fluids from clinical bacterial pneumonia or experimental endotoxin-induced mastitis lesions. Finally, intramuscular or subcutaneous application of CXCL8((3-73))K11R/G31P (75 micro g/kg) reduced by up to 97% neutrophil infiltration into intradermal endotoxin challenge sites in cattle, and prevented their circulating neutrophils from responding to CXCL8/IL-8 or ENA-78 in vitro. This data thus encourages further investigation of the potential impact of this novel antagonist on ELR-CXC chemokine-driven inflammatory disorders.
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PMID:CXCL8((3-73))K11R/G31P antagonizes the neutrophil chemoattractants present in pasteurellosis and mastitis lesions and abrogates neutrophil influx into intradermal endotoxin challenge sites in vivo. 1240 56

Lung tissue removed from neonatal calves with acute Mannheimia haemolytica pneumonia showed that rapid up-regulation of the basal mRNA expression of tracheal antimicrobial peptide (TAP), NF-kappa B, and intercellular adhesion molecule 1 occurred after infection; TAP and interleukin 8 expression were highly correlated. This work suggests that the coordinated expression of beta-defensin and inflammatory elements occurs during bacterial pneumonia.
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PMID:Coordinated expression of tracheal antimicrobial peptide and inflammatory-response elements in the lungs of neonatal calves with acute bacterial pneumonia. 1270 77

We analyzed the characteristics of the inflammatory response occurring in blood during pulmonary infections in human immunodeficiency virus (HIV)-infected patients. A prospective study of consecutive hospital admissions of HIV-infected patients with new-onset radiologic pulmonary infiltrates was carried out in a tertiary university hospital from April 1998 to May 2001. Plasma cyclic AMP receptor protein (CRP), interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, and tumor necrosis factor alpha (TNF-alpha) levels were determined at the time of admission and 4, 5, and 6 days later. Patients were included in a protocol addressed to study etiology and outcome of disease. A total of 249 episodes of infection were included, with the main diagnoses being bacterial pneumonia (BP) (118 episodes), Pneumocystis carinii pneumonia (PCP) (41 episodes), and mycobacteriosis (36 episodes). For these three patient groups, at the time of admission the median CRP and cytokine levels were as follows: CRP, 10.2, 3.8 and 5 mg/dl, respectively (P = 0.0001); IL-8, 19, 3, and 2.9 pg/ml (P = 0.045); and TNF-alpha, 46.4, 44, and 75 pg/ml, respectively (P = 0.029). There were no significant differences in levels of IL-1beta, IL-6, or IL-10 among the patient groups. A total of 23 patients died. At the time of admission, HIV-infected patients with BP had higher plasma CRP and IL-8 levels than did PCP and mycobacteriosis patients. TNF-alpha levels were higher in patients with mycobacteriosis. An elevated IL-8 level (>61 pg/ml) at the time of admission was an independent factor associated with higher mortality (odds ratio, 12; 95% confidence interval, 1.2 to 235.5).
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PMID:Inflammatory responses in blood samples of human immunodeficiency virus-infected patients with pulmonary infections. 1513 89

Cyclosporin A (CsA) blocks T cell activation by interfering with the Ca2+-dependent phosphatase, calcineurin. Proinflammatory responses to bacteria that are activated by Ca2+-fluxes in airway cells are a potential target for CsA. Although local immunosuppression may be advantageous to control airway inflammation, it could also increase susceptibility to bacterial pneumonia and invasive infection. As aerosolized CsA is currently under study in lung transplantation, we examined its direct effects on airway cells as well as in a murine model of pneumonia. Epithelial interleukin-6 production was very effectively inhibited by CsA, whereas CXCL8 production, the major PMN chemokine, was only modestly diminished. Responses to a TLR2 agonist Pam3Cys were more sensitive to CsA inhibition than those activated by Pseudomonas aeruginosa. CsA substantially blocked activation of nuclear factor of activated T cells and cAMP-responsive element-binding protein (P<0.001), inhibited CCAAT/enhancer-binding protein by 50% (P<0.05), and minimally blocked activator protein-1 and nuclear factor-kappaB responses to bacteria in epithelial cells. The in vitro effects were confirmed in a mouse model of P. aeruginosa infection with similar rates of PMN recruitment, pneumonia and mortality in CsA treated and control mice. These studies indicate that airway epithelial signaling is a potential target for CsA, and such local immunosuppression may not increase susceptibility to invasive infection.
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PMID:The effect of cyclosporin A on airway cell proinflammatory signaling and pneumonia. 1587 61

The ELR-CXC chemokines play important roles in neutrophilic inflammation. We report in this study that a fully human ELR-CXC chemokine antagonist that we have generated, CXCL8((3-72))K11R/G31P (G31P), has potent anti-inflammatory effects that arise through its actions at multiple levels. G31P inhibited CXCL8-induced chemotactic responses and intracellular Ca(2+) flux in CXCR1-transfected HEK cells and neutrophils, and responses of neutrophils to CXCR2-exclusive ligands. G31P desensitized heterologous G protein-coupled receptors on neutrophils, 52-86% reducing their Ca(2+) flux and chemotactic responses to leukotriene B(4), C5a, and the bacterial tripeptide fMLP. G31P also 60-90% blocked neutrophil chemotactic responses to mediators present in 10 of 12 sputum samples from cystic fibrosis or bronchiectasis subjects with bacterial pneumonia. Moreover, whereas A549 bronchial epithelial cells (which expressed CXCR1) secreted approximately 29,000 pg/ml CXCL8 in response to in vitro endotoxin challenge, G31P reduced this response by up to 98%, presumably by interrupting an autocrine inflammatory loop. The anti-inflammatory effects of G31P extended also to reversing the antiapoptotic influence of ELR-CXC chemokines on neutrophils. That these effects were relevant in vivo was confirmed in a guinea pig model of airway endotoxemia, wherein the human form of G31P >95% blocked neutrophil infiltration into and activation within the airways, as determined by airway levels of the neutrophil primary, secondary, and tertiary granule markers myeloperoxidase, lactoferrin, and matrix metalloproteinase-9, respectively, and the epithelial cell marker matrix metalloproteinase-2. These data suggest that the beneficial effects of ELR-CXC chemokine antagonism arise through effects that occur at multiple levels, including epithelial cells, neutrophils, and alternate G protein-coupled receptors.
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PMID:ELR-CXC chemokine receptor antagonism targets inflammatory responses at multiple levels. 1923 19


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