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)

Eosinophilia and eosinophil function are regulated by cytokines such as granulocyte/macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and interleukin-5 (IL-5). We have investigated the modulatory role of IL-5 on N-formyl-methionyl-leucyl-phenylalanine (FMLP), neutrophil-activating factor (NAF/IL-8), platelet factor 4 (PF4), and cytokine-induced chemotaxis of eosinophils from normal individuals. These eosinophils show a small chemotactic response toward PF4 but not to NAF/IL-8 and FMLP. Preincubation of eosinophils with low concentrations of IL-5 caused significantly increased responses toward PF4 and induced a significant chemotactic response toward FMLP and NAF/IL-8. In marked contrast, IL-5 (or IL-3) priming of eosinophils from normal donors resulted in a strong inhibition of GM-CSF-induced chemotaxis. A similar decrease in the chemotactic response toward GM-CSF was observed in eosinophils derived from allergic asthmatic individuals. This finding suggests that the latter eosinophils may have had a prior exposure to IL-5 (or IL-3). Washing of the cells after priming did not abrogate the inhibition of the GM-CSF response. Our data indicate that at low concentrations IL-5 is an important modulator of eosinophil chemotaxis, causing selective upregulation or downregulation of chemotactic responses toward different agents.
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PMID:Modulation of eosinophil chemotaxis by interleukin-5. 144 9

Eosinophilia and eosinophil function are regulated by cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-5. We have investigated the modulatory role of GM-CSF and IL-3 on the platelet-activating factor (PAF)-, neutrophil-activating factor (NAF/IL-8)-, leukotriene B4 (LTB4)-, N-formyl-methionyl-leucyl-phenylalanine (FMLP)-, and human complement factor C5a-induced chemotaxis of eosinophils from normal individuals. These eosinophils show a chemotactic response toward PAF, LTB4, and C5a, but not to NAF/IL-8 and FMLP. Preincubation of the eosinophils with picomolar concentrations of GM-CSF caused a significant increase in the response toward LTB4 and induced a significant chemotactic response toward NAF/IL-8 and FMLP. Preincubation of the eosinophils with picomolar concentrations of IL-3 also induced a chemotactic response toward NAF/IL-8 and FMLP, and enhanced the PAF-induced chemotaxis response toward C5a was not influenced by both cytokines. Nanomolar concentrations of GM-CSF or IL-3 caused a significant inhibition of the C5a-induced chemotaxis. The LTB4-induced chemotaxis was also significantly inhibited in case of GM-CSF. At these concentrations both GM-CSF and IL-3 acted as chemotaxins for eosinophils were washed after pretreatment with GM-CSF and IL-3 the potentiation of the chemotactic response remained, whereas the inhibitory mode of action disappeared. Our data indicate that at picomolar concentrations the cytokines GM-CSF and IL-3 can modulate eosinophil chemotaxis and at nanomolar concentrations these cytokines can act as chemotaxins for eosinophils.
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PMID:Modulation and induction of eosinophil chemotaxis by granulocyte-macrophage colony-stimulating factor and interleukin-3. 164 45

Hyper-IgE syndrome is a rare immunodeficient disorder characterized by recurrent severe staphylococcal infections of the skin and sinopulmonary tract, chronic eczematoid rashes, coarse facial features, mild eosinophilia, and markedly elevated serum IgE levels. Hyperimmunoglobulinemia D, depressed DTH, and varying degrees of pathogenesis of this syndrome is unknown. The clinical manifestations and the recent research findings indicated the followings: 1) increased production of IL-4: hyperimmunoglobulinemia E, increased number of Fc epsilon R(+)-cells in peripheral blood, 2) defective production of IFN-gamma: abnormal local inflammatory responses (formation of cold abscesses), chemotactic defect in the circulating neutrophils (abnormalities in IFN-gamma/IL-8 pathway), depressed DTH, 3) T-cell immunodeficiency?-chronic dermatitis? 4) genetic factors (frequent familial occurrence, characteristic facial appearance with broad nasal bridge). These observations led us to postulate that both the increased production of IL-4 and the defective production of IFN-gamma may be the immunopathological bases of this syndrome. Recently, these cytokines were demonstrated to be secreted by different subsets of helper T-cells, designated TH1 and TH2, in murine system, suggesting that the regulatory imbalances between IL-4 and IFN-gamma in this syndrome might be due to the differential activation or inactivation of these helper T-cell subsets.
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PMID:[Hyper IgE syndrome--a disease of imbalanced activation of helper T-cell subsets?]. 214 8

Increasing evidence suggests a role for activated T cells and cytokines in the regulation of eosinophilic inflammation in asthma. In this study, we investigated the distribution of leukocytes, lymphocytes, their activation state, and the cytokine profile in BAL from 10 atopic asthmatics with positive skin prick tests and elevated specific IgE levels to birch or grass pollen. Using segmental allergen challenge, 250 PNU of the appropriate allergen or saline were instilled into different segments, which were lavaged 10 min (10 min) and 18 h (18 h) after allergen challenge or 18 h after saline challenge (C). In peripheral blood the number of neutrophils and activated IL-2R+/CD4+ T cells increased significantly 18 h after allergen provocation; there was no change in eosinophils, other leukocytes, or lymphocyte subsets. In contrast, numbers of eosinophils, neutrophils, and IL-2R+/CD4+ T cells increased significantly in BAL samples at 18 h. The numbers of neutrophils and eosinophils were not significantly different in the lavage performed at 10 min and at C. Analysis of cytokines in concentrated BAL fluid revealed significantly increased levels of IL-5, IL-2, IL-1, TNF-alpha, IL-6, IL-8, and GM-CSF, but not of IL-4 and IFN-gamma at 18 h compared with those at C and at 10 min. The correlation between IL-5 levels, eosinophil numbers, and activated T cells supports a role for T-cell-derived IL-5 in causing tissue eosinophilia in allergic asthma.
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PMID:T cells and cytokines in bronchoalveolar lavage fluid after segmental allergen provocation in atopic asthma. 769 73

Interleukin-8 (IL-8), a potent pro-inflammatory cytokine, has been shown to have chemotactic activity for neutrophils, lymphocytes, and basophils. Effects of IL-8 on eosinophil chemotaxis are unresolved. Because eosinophils accumulate at the site of allergic inflammation and may play a role in the pathogenesis of asthma, we investigated the eosinophilotactic capacity of IL-8. We examined the ability of IL-8 to induce human eosinophil migration across 3-microns pore naked filters, and human umbilical vein endothelial cell and human pulmonary type II-like epithelial cell (A549) monolayers cultured on these filters. IL-8 induced similar dose-related eosinophil migration through all three barriers. Kinetic experiments indicated more rapid migration through noncellular barriers but equivalent migration through all barriers by 3 h. Chemotactic/chemokinetic data show that IL-8-induced eosinophil migration is chemotactic. We also determined that the ability of IL-8 to induce transcellular migration was unique in comparison with other cytokines and was not dependent on the use of fresh vs. passaged monolayer cells as barriers. Therefore our data indicate that IL-8 may play a significant role in tissue eosinophilia observed in allergic respiratory diseases.
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PMID:Interleukin-8 is a potent mediator of eosinophil chemotaxis through endothelium and epithelium. 784 Feb 16

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

In the present study we evaluated the haematological and immunological changes in 4 patients with advanced melanoma and 6 patients with advanced renal cell carcinoma treated with subcutaneous interleukin (IL)-2 and interferon (IFN)-alfa-2b. Serum samples taken before and during six weeks' courses of IL-2 plus IFN-alfa were assayed for the presence of IL-2, soluble IL-2-receptor (sIL-2R), soluble intercellular adhesion molecule-1 (sICAM-1), IL-6 and IL-8. In addition, whole blood counts were taken. Eosinophilia occurred in all patients, lymphocytosis in 8 patients. The higher maximum level of IL-2 during treatment seemed to be connected to longer survival: it was a median of 578 pg/ml in the patients with a median survival of 7 months, and 1025 pg/ml in the patients who survived a median of 15 months. Conversely, an increase in sIL-2R was an unfavourable sign: it was a median of 8-fold and 3-fold in the patients with a median survival of 7 and 16 months, respectively. During treatment, sICAM-1 levels paralleled with those of sIL-2R. There was major intraindividual and interindividual variation in serum IL-6 and IL-8 levels with no distinctive kinetic pattern. Thus, no definite conclusions could be drawn. However, it seems worthwhile to measure IL-2, sIL-2R and sICAM-1 during immunotherapy; their prognostic value should be further evaluated in a larger patient population.
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PMID:Serum levels of interleukins 2, 6 and 8, soluble interleukin-2 receptor and intercellular adhesion molecule-1 during treatment with interleukin-2 plus interferon-alfa. 887 89

We have applied the technique of sputum induction by hypertonic saline in asthmatics and nonatopic control subjects to study an array of indices of airway inflammation believed to be relevant to asthma pathogenesis. Compatible with a central role for eosinophils and mast cells in asthma, sputum of asthmatic subjects contained increased numbers of eosinophils and levels of eosinophil cationic protein (ECP) and mast cell tryptase. Eosinophil numbers, and ECP and histamine levels correlated with the degree of methacholine airways responsiveness, and ECP, tryptase, and histamine correlated with raised concentrations of albumin. Using the micro-Boyden chamber technique eosinophil chemotactic activity was identified only in the sputum from asthmatics. The correlation between the raised levels of total IgA, IL-8/IgA complexes, and tryptase and the degree of sputum eosinophilia and ECP levels, suggests possible mechanisms for eosinophil chemotaxis and activation in asthma. Row cytometric analysis of sputum lymphocytes showed an increase in CD4+ T cells and T cells expressing intercellular adhesion molecule-1 (ICAM-1) in asthma which, together with the finding of raised levels of soluble ICAM-1 in the sputum, indicates upregulation of this adhesion molecule. Finally, the proportion of CD16+ natural killer (NK) cells was reduced in the sputum of asthmatics. These observations highlight the importance of the airway inflammation in causing asthma and further confirm the usefulness of sputum induction as a tool in asthma research.
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PMID:Cell infiltration, ICAM-1 expression, and eosinophil chemotactic activity in asthmatic sputum. 903 80

Eosinophilia is a feature of nasal polyposis. The aim of this study was to determine the role of cytokines and allergen in maintaining the eosinophilic infiltrate in this condition. Polyp fragments from house dust mite (HDM)-sensitive atopic individuals and nonatopic individuals were cultured in the presence of HDM, or phytohaemagglutinin (PHA) or culture medium alone. Culture supernatants were assayed for interleukins (IL) 3, 5, and 8 and granulocyte macrophage colony stimulating factor (GM-CSF), and eosinophil survival enhancing activity (ESEA) in vitro. Significant ESEA was produced spontaneously. When polyp tissue from atopics, but not from nonatopics, was stimulated with allergen for 2 days there was a further increase in ESEA associated with a median 12 and fourfold increase in IL-8 and GM-CSF, respectively. This increased ESEA was markedly reduced with anti-GM-CSF and, to a lesser extent, anti-IL-8 blocking antibodies. When stimulated with PHA, polyp tissue from atopic subjects also produced increased ESEA, implicating possible T-cell involvement. This was associated with a small (twofold), but significant, increase in IL-8 and a less consistent increase in GM-CSF. However, anti-IL-8 or anti-GM-CSF blocking antibodies failed to reduce the ESEA in these supernatants, suggesting involvement of other mechanisms. This study suggests that in sensitized individuals, allergen may contribute to polyp eosinophilia by stimulating the production of granulocyte/macrophage colony stimulating factor and interleukin 8.
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PMID:Allergen-induced release of GM-CSF and IL-8 in vitro by nasal polyp tissue from atopic subjects prolongs eosinophil survival. 923 Feb 33

Apart from ventilatory and bacteriologic aspects, understanding the pathomechanisms of inflammation in chronic sinusitis and nasal polyposis seems crucial for further success in disease treatment. New insights into inflammatory processes became recently possible by investigating the pattern of cytokines and chemokines as well as adhesion molecules in different acute and chronic sinus diseases. The proinflammatory cytokines interleukin (IL)-1 beta, IL-6 and especially the neutrophil-chemoattractant IL-8 play a dominant role in acute sinusitis, as was shown before for viral and allergic rhinitis. In contrast, IL-3 protein dominates the cytokine profile in chronic sinusitis, giving support to a variety of inflammatory cells. The most striking finding was the increased synthesis of IL-5 protein in bilateral nasal polyposis, whereas IL-5 was not found in controls or antrochoanal polyps. As this cytokine is known to enhance eosinophil activation and survival, our data point to IL-5 as a key protein in the pathomechanism of tissue eosinophilia in nasal polyposis. The investigation of cytokine patterns may furthermore help to differentiate between sinusitis subgroups, e.g. in the classification of sinus diseases.
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PMID:Inflammatory mechanisms in chronic sinusitis. 944 69


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