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)

Idiopathic pulmonary fibrosis is an immunologically mediated pulmonary disorder in which activated alveolar macrophages (AM) and neutrophils play cardinal roles in the pathogenesis of the inflammatory lung lesion. The factors responsible for the induction and perpetuation of the neutrophilic alveolitis are not known. Recently, a novel cytokine (Interleukin-8) was described that is released by activated mononuclear phagocytes and a variety of other cell types, and it exhibits potent chemotactic activity for polymorphonuclear leukocytes (PMN). Increased expression of IL-8 has been described in other inflammatory disorders characterized by neutrophilic infiltration, including psoriasis, rheumatoid arthritis, and the sepsis syndrome, but no studies have assessed this cytokine in the context of interstitial pulmonary disorders. We have previously shown that normal human AM release IL-8 upon appropriate stimulation, but data assessing the expression of IL-8 by human AM in specific pulmonary disease states are lacking. In this study, we examined the expression of steady-state mRNA for IL-8 by human alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis and from healthy volunteers. Because it is known that adherence to plastic culture plates may up-regulate gene expression for IL-8 in the absence of additional stimulation, we extracted mRNA immediately from the cell pellet obtained by BAL rather than using cultured alveolar macrophage monolayers. Northern blot analysis was performed to determine IL-8 mRNA expression. We found that BAL cells from patients with IPF constitutively expressed mRNA for IL-8, and the amount of IL-8 mRNA (as assessed by laser densitometry) correlated with the percent of neutrophils on BAL.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Neutrophilic alveolitis in idiopathic pulmonary fibrosis. The role of interleukin-8. 159 15

NAF/NAP-1 is a novel tissue-derived chemotactic peptide. It consists of 72 amino acids and has no sequence homology to known cytokines. NAF/NAP-1 is produced by a wide variety of cells after stimulation with interleukin-1, tumor necrosis factor or endotoxin, and has the properties of a local mediator of neutrophil recruitment into diseased tissues. There are indications that NAF/NAP-1 is important in the pathophysiology of inflammatory conditions such as psoriasis, idiopathic pulmonary fibrosis, asbestosis, adult respiratory distress syndrome and different forms of arthritis.
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PMID:[Naf/nap-1, a new peptide which activates neutrophil leukocytes]. 268 5

We estimated defensins, antimicrobial and cytotoxic peptides localized in azurophil granules of neutrophils, in bronchoalveolar lavage fluid (BALF) in patients with diffuse panbronchiolitis (DPB). BALF from DPB patients contained a higher concentration of defensins than those from patients with idiopathic pulmonary fibrosis and healthy volunteers. A significant correlation was observed between the concentration of defensins and the number of neutrophils, the concentration of interleukin-8 or neutrophil elastase in BALF of DPB patients. An immunohistochemical defensins in neutrophils and mucinous exudates in the airways and in the surface of bronchiolar epithelial cells. After treatment with macrolide antibiotics, significant reductions in the concentrations of defensins, IL-8 and neutrophil numbers in BALF of DPB patients were observed. These findings suggest that the lung injury in DPB could be caused by defensins released by neutrophils accumulated in the airways.
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PMID:[A study of defensins in bronchoalveolar lavage fluid in patients with diffuse panbronchiolitis]. 759 98

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.
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PMID:Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. 792 34

A variety of cytokines have been implicated in the pathogenesis of pulmonary sarcoidosis, but the exact roles of IL-6 and IL-8 are not yet clear. We studied these cytokine levels in BALF from patients with pulmonary sarcoidosis, idiopathic pulmonary fibrosis (IPF), systemic screlosis (SSc) with interstitial lung disease and control subjects. IL-6 and IL-8 levels were significantly elevated in sarcoidosis, IPF and SSc with interstitial lung disease compared with control subjects. Subjects with sarcoidosis had significantly increased levels of both cytokines compared with controls when the cytokine values were corrected by the total albumin content and the two cytokine levels correlated with each other (r = 0.876). BALF IL-6 levels correlated with percent lymphocytes and percent CD3+ cells. Moreover, when sarcoidosis patients were divided into three groups, those who needed steroid therapy or had progressive disease showed increased cytokine levels in BALF over stable or improved patients. These observations suggest that locally derived IL-6 and IL-8 were increased in sarcoidosis and correlated with activity of this granulomatous lung disease.
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PMID:Increased IL-6 and IL-8 in bronchoalveolar lavage fluids (BALF) from patients with sarcoidosis: correlation with the clinical parameters. 901 Feb 73

We measured the levels of defensins, antimicrobial peptides, and cytotoxic peptides in azurophil granules of neutrophils in plasma, and in bronchoalveolar lavage fluid (BALF) from patients with the acute respiratory distress syndrome (ARDS). High levels of plasma defensins were observed in samples from patients with ARDS. Samples of BALF from patients with ARDS also had more neutrophils and higher concentrations of defensins than did samples from healthy volunteers and from patients with idiopathic pulmonary fibrosis or diffuse panbronchiolitis. In addition, the concentration of interleukin (IL)-8 in BALF was higher in patients with ARDS than in other subjects. A significant correlation was found between the concentration of defensins and that of IL-8 in BALF from patients with ARDS. These findings suggest that the lung injury in ARDS is caused by defensins released by neutrophils that accumulate in the lungs.
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PMID:[Defensin in plasma and in bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome]. 902 18

Neutrophil accumulation in the lower respiratory tract of patients with fibrosing alveolitis is thought to be facilitated by IL-8, a neutrophil chemoattractant primarily secreted by mononuclear phagocytes. The aims of this study were: (i) to explore IL-8 secretion by lung and blood mononuclear phagocytes in subjects with cryptogenic fibrosing alveolitis, systemic sclerosis with and without fibrosing alveolitis, sarcoidosis and normal individuals; (ii) to examine IL-8 secretory heterogeneity in alveolar macrophages and peripheral blood monocytes; and (iii) to correlate alveolar macrophage phenotypic profile to IL-8 secretion. We observed that more monocytes secreted IL-8 than autologous macrophages and that there was heterogeneity in the in vitro IL-8 secretion by alveolar macrophages and peripheral blood monocytes. IL-8 secretion by alveolar macrophages was significantly higher in subjects with fibrosing alveolitis compared with subjects without fibrosing alveolitis, due to a higher percentage of IL-8-secreting alveolar macrophages in the fibrotic group both in the absence (P < 0.002) and presence of lipopolysaccharide (LPS) (P < 0.04) and correlated with bronchoalveolar lavage neutrophil percentage. Using the MoAbs RFD1, RFD7 and RFD9, that distinguish subsets of alveolar macrophages, we have been able to identify associations between secretion of IL-8 and smaller cells and the cells identified by the MoAb RFD7. In situ hybridization of the bronchoalveolar lavage cell population revealed that alveolar macrophages are the predominant source of IL-8 in the lung. We conclude that there is an increased number of IL-8-secreting alveolar macrophages in the lungs of patients with fibrosing alveolitis, and IL-8 secretion by these cells is associated with specific phenotypic profile expression.
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PMID:Up-regulation of IL-8 secretion by alveolar macrophages from patients with fibrosing alveolitis: a subpopulation analysis. 909 17

Idiopathic pulmonary fibrosis (IPF) is a chronic and often fatal disorder. Fibroplasia and deposition of extracellular matrix are dependent, in part, on angiogenesis. We postulated that an imbalance exists in the expression of angiogenic (IL-8) vs angiostatic (IFN-gamma-inducible protein (IP-10)) CXC chemokines, which favors net angiogenesis in IPF. To test this hypothesis, we obtained open lung biopsies either from normal patients undergoing thoracic surgery for reasons other than interstitial lung disease (control) or from patients with IPF. We found that levels of IL-8 were greater from tissue specimens of IPF patients then from those of controls. In contrast, IP-10 levels were higher from tissue specimens obtained from control subjects than from those from IPF patients. When IL-8 or IP-10 was depleted from IPF tissue specimens, tissue-derived angiogenic activity was markedly reduced or enhanced, respectively. Immunolocalization of IL-8 demonstrated that the pulmonary fibroblast (PF) of IPF lung was the predominant cellular source of IL-8. Isolated PF from IPF patients constitutively produced more IL-8 and less IP-10 than control PF. Conditioned media from IPF-PFs demonstrated constitutive angiogenic activity that was attributable, in part, to IL-8. Depletion of IP-10 from IPF-PF CM resulted in an increase in corneal neovascularization. These findings support the notion that IL-8 and IP-10 are important factors that regulate angiogenic activity in IPF.
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PMID:The CXC chemokines, IL-8 and IP-10, regulate angiogenic activity in idiopathic pulmonary fibrosis. 923 41

This study was designed to clarify the contribution of IL-8 as a specific neutrophil chemotactic factor in the human respiratory tract in various pulmonary diseases. The neutrophil chemotactic activity (NCA), neutrophil counts and IL-8 concentration in the bronchoalveolar lavage fluid (BALF) obtained from normal volunteers (NV), control patients (CP), patients with diffuse panbronchiolitis (DPB) and patients with idiopathic pulmonary fibrosis (IPF) were examined. Neutrophil counts, NCA and IL-8 concentration in BALF obtained from patients with DPB or IPF was significantly higher than that from NV or CP. The IL-8 concentration correlated with neutrophil count and also correlated with NCA in BALF from patients with IPF, whereas there was no correlation between these factors in BALF from DPB. These results suggest that the contribution of IL-8 to neutrophil accumulation of the lower respiratory tract is different between IPF and DPB.
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PMID:Interleukin-8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis or idiopathic pulmonary fibrosis. 939 18

It has been shown that interleukin 8 (IL-8) is increased in bronchoalveolar lavage fluid (BALF) of patients with idiopathic pulmonary fibrosis (IPF) and there is increasing evidence that it is involved in the pathogenesis of this disease. To date, no data are available as to whether IL-8 is elevated in sera of IPF patients. We obtained sera from 42 patients with IPF and 20 healthy controls at time of BAL. From 20 of 42 patients with IPF and 12 of 20 controls BALF was available, enabling us to measure IL-8 in serum and BALF of the same time point. IL-8 was significantly elevated in serum (54.7 +/- 7.5 pg/ml, p < 0.0001) and BALF (715.7 +/- 112.4 pg/ml, p < 0.0001) of patients with IPF compared with controls (IL-8 in serum, 5.2 +/- 0.8 pg/ml; IL-8 in BALF, 67.3 +/- 9.7 pg/ml). We observed a significant positive correlation between IL-8 levels in BALF and percentage of BALF neutrophils (p < 0.001) and between serum IL-8 and BALF IL-8 levels (p < 0.005) in patients with IPF. Consequently, the serum IL-8 level correlated positively with the percentage of BAL neutrophils (p < 0.01), indicating that it may reflect the degree of neutrophilic alveolitis in IPF. Furthermore, the serum IL-8 level showed a negative correlation with important indicators of impairment of lung function (DL(CO), TLC, VC) and PaO2. In conclusion, we were able to demonstrate that the degree of neutrophilic alveolitis in IPF is reflected by increased serum levels of IL-8 and we suggest that the serological assessment of IL-8 may provide a useful parameter for clinicians in monitoring patients with IPF.
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PMID:Serum level of interleukin 8 is elevated in idiopathic pulmonary fibrosis and indicates disease activity. 951 88


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