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)

Cytokines and cell adhesion receptors play a pivotal role in the recruitment of cells from the peripheral blood into inflamed tissue. Allergic rhinitis has previously been described as an inflammatory reaction characterised by the migration of granulocytes into the nasal mucosa. Using this model, we investigated the release of proinflammatory cytokines (interleukin IL-1 beta, IL-6, IL-8 and tumour necrosis factor-alpha TNF-alpha) and the expression of cell adhesion molecules (ELAM-1, ICAM-1 and LFA-1) in two studies involving biopsies as well as lavage and brush techniques. IL-1 beta and TNF-alpha can be found rapidly after allergen exposure and seem to initiate the cellular infiltration. The release of the chemokine IL-8 correlates with the continuously increasing number of granulocytes on the mucosal surface. Allergic rhinitis subjects showed significantly increased secretion levels of the proinflammatory cytokines IL-1 beta and IL-6 and of the chemokine IL-8. These findings correspond to a higher expression of the adhesion receptors ELAM-1, ICAM-1 and LFA-1 in allergic mucosa. We conclude that proinflammatory cytokines regulate the cell infiltration by the induction of adhesion receptor expression.
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PMID:[The role of pro-inflammatory cytokines in recruiting inflammatory cells in the nose]. 751 83

Allergic diseases such as allergen-induced rhinitis represent an inflammatory reaction that is characterized by the chemotaxis and activation of various cell populations. A high degree of cell-to-cell communication is needed to orchestrate this inflammatory immune response. A variety of cytokines and adhesion receptors seem to play an important role in the allergic late phase reaction. Here we demonstrate that proinflammatory cytokines such as interleukin(IL)-1, IL-8 and TNF-alpha (tumor necrosis factor-alpha) can be detected in nasal secretions and mucosa by enzyme-linked immunosorbent assay and immunohistochemistry. The increased expression of adhesion receptors in mucosa specimens of patients with seasonal allergic rhinitis points to their role in regulating the cellular migration and probably represents a key event in allergic inflammation. We established an in vitro model using freshly taken nasal mucosa to study the induction of adhesion receptors by proinflammatory cytokines. E-selectin, an endothelial receptor, was strongly upregulated by IL-1 beta, TNF-alpha and allergen. The induction due to allergen exposure of the mucosa was markedly inhibited by soluble cytokine receptors (sIL-1R, TNF-BP) or by a receptor antagonist (IL-1ra) and prednisolone, These findings indicate that proinflammatory cytokines may be key factors for the upregulation of adhesion processes in human nasal mucosa and the activation of various cell populations involved in the allergic inflammation. They therefore represent a main target for new therapeutic strategies.
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PMID:Proinflammatory cytokines in allergic rhinitis. 753 66

We recently demonstrated that interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-6 and IL-8 can be found in nasal secretions from allergic rhinitis patients under artificial and natural conditions. By ELISA measurements, significantly elevated baseline levels for IL-1 beta, IL-6 and IL-8 were found in seasonal allergic compared to control subjects. Within the first 2 h after nasal allergen challenge, IL-1 beta and TNF are secreted, whereas IL-6 and IL-8 showed a slow increase over 6-8 h. All cytokine levels returned to baseline within 24 h after exposure. Repeated measurements at 4-week intervals in perennial allergic rhinitis subjects (n = 27) showed significant correlations between IL-1 and IL-8, IL-6 and IL-8 and IL-6 and the symptom score (visual analogue scale). The IL-1 receptor antagonist IL-1ra was found in great molar excess in the secretions and correlated significantly with IL-8, but not IL-1 beta. In an in vitro assay using fresh nasal mucosa of grass-pollen-allergic subjects, we were able to demonstrate a strong and rapid induction of E-selectin adhesion receptor expression on endothelial cells by allergen, IL-1 beta and TNF. The adhesion receptor expression was markedly inhibited by soluble IL-1 receptors, sTNF-R and IL-1ra. These data indicate a key role for inflammatory cytokines in the regulation of allergic inflammation.
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PMID:Proinflammatory cytokines: measurement in nasal secretion and induction of adhesion receptor expression. 754 54

Human mast cells can be divided into two distinct phenotypes based on their content of neutral serine proteases, suggesting that they serve differing biologic and pathologic roles. Recently, it has been demonstrated that human mast cells are a source of several pleiotropic cytokines including IL-4, IL-5, IL-6, IL-8, and TNF-alpha, but not all mast cells contain all of these cytokines, suggesting that there is also functional heterogeneity with respect to cytokine expression. In this study, we have examined the relationship between mast cell neutral protease expression and cytokine content using immunohistochemistry. Bronchial mucosal biopsies from five normal subjects and five patients with allergic asthma, and nasal mucosal biopsies from five normal subjects and three patients with allergic rhinitis were embedded in glycol methacrylate. Sections (2 microns) were stained for IL-4, IL-5, and IL-6, adjacent to serial sections stained for tryptase and chymase. The distribution of cytokines among the tryptase+ chymase- mast cells (MCT) and tryptase+ chymase+ mast cells (MCTC) was examined by co-localization of cytokines to MCTC or MCT in serial sections using the camera-lucida. Although IL-4 was distributed among both mast cell phenotypes, it was expressed preferentially by the MCTC subset (overall 85% MCTC:15% MCT). In contrast, IL-5 and IL-6 were restricted almost exclusively to the MCT subset. Immunostaining of isolated skin mast cells (> 99% MCTC) supported these findings, with strong immunoreactivity present for IL-4 but very little for IL-5 or IL-6. These results indicate that in addition to exhibiting heterogeneity with respect to neutral protease content of the secretory granules, human mast cells are also heterogeneous with respect to cytokine content. This suggests that the biologic functions of MCTC and MCT cells differ as a result of their capacity to generate and release different cytokine profiles.
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PMID:Heterogeneity of human mast cells based on cytokine content. 760 7

Recent studies have suggested that exposure to air pollutants may sensitise susceptible individuals to allergen. We have investigated the effect of exposure for 6 h to 400 ppb NO2 on nasal airways resistance (NAR) and changes in inflammatory mediators (IMs) in nasal lavage in subjects with a history of seasonal allergic rhinitis. In this single blind crossover study, 8 patients were randomised to exposure to either air or 400 ppb NO2 in air and evaluated for changes in NAR and IM, before and after exposure. Another 8 patients were further challenged with allergen after similar exposure regimes and then evaluated for changes in NAR and IMs. Exposure to air or NO2 did not alter either NAR or the levels of eosinophil cationic protein (ECP), mast cell tryptase (MCT), myeloperoxidase (MPO) or interleukin (IL)-8 in nasal lavage. MCT was significantly increased after allergen challenge following exposure to both air and NO2. In contrast, ECP was significantly increased by allergen challenge only after exposure to NO2. Neither MPO nor IL-8 were altered after allergen challenge. These results suggest that NO2 may increase eosinophil activation in the early-phase response to nasal allergen provocation in allergic rhinitis.
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PMID:Nitrogen dioxide increases eosinophil activation in the early-phase response to nasal allergen provocation. 761 14

Accumulation of mast cells and eosinophils in the nasal epithelial layer occurs in nasal allergic reactions and nasal polyps. We have already demonstrated that fluticasone propionate (FP) inhibits the accumulation of mast cells and eosinophils locally, and also improves the nasal symptoms of patients with allergic rhinitis. We hypothesized that cytokines generated from nasal epithelial cells possibly contribute to the accumulation of cells and eosinophils in the nasal epithelial layer. In this experiment we examined the inhibitory effect of FP on the production of GM-CSF, IL-6 and IL-8 by culturing of nasal epithelial cells in vitro. Our results show that FP significantly reduces the level of GM-CSF, IL-6 and IL-8 in the supernatant of culture media of nasal epithelial cells for a period of 6 days. In addition, preincubation of nasal epithelial cells with FP for 6 days causes a significant reduction of GM-CSF levels in the supernatant of culture-media of cultured nasal epithelial cells during the subsequent period of 6 days without FP. These results provide evidence that FP inhibits the accumulation of mast cells and eosinophils in the mucoepithelial layer of the nasal membrane.
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PMID:[Fluticasone propionate reduced the production of GM-CSF, IL-6 and IL-8 generated from cultured nasal epithelial cells]. 819 53

Allergic mucosal inflammation is characterized by the presence of cell infiltration, predominantly with IgE-sensitized mast cells and activated eosinophils, and appears to be regulated by the local production and release of several cytokines, particularly IL-4 and IL-5. Although attention has focused on the Th2 subpopulation of CD4+ T lymphocytes as an important source of these cytokines, human mast cells have been shown to both store and secrete IL-4 and TNF-alpha. To investigate the expression of cytokines relevant to allergic inflammation and to identify their cellular localization within the nasal mucosa, we have undertaken specific immunohistochemical staining of thin sections of inferior turbinate biopsies from patients with perennial allergic rhinitis and, for comparison, from nonatopic healthy volunteers. The cytokines investigated were IL-4, IL-5, IL-6, and IL-8. In both the normal and rhinitic biopsies numerous cells immunoreactive for IL-4, IL-5, and IL-6 were seen. Staining of adjacent 2-microns sections for CD3, mast cell tryptase, and eosinophil cationic protein revealed that 90% of the IL-4 immunoreactive cells were mast cells, with biopsies from rhinitic subjects containing significantly more IL-4+ cells than biopsies from normal controls (p = 0.02), especially when assessed with the anti-IL-4 mAb 3H4. Mast cells also accounted for > 90% of IL-6 and > 50% of IL-5 immunoreactive cells. IL-5 immunoreactivity was also localized to eosinophils, whereas IL-8 localized predominantly to the nasal epithelium in both groups. No cytokines were found in association with T lymphocytes. These findings indicate that the mast cell is an important source of preformed cytokines and as such may contribute to the chronicity of the mucosal inflammation that characterizes allergic rhinitis.
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PMID:Immunolocalization of cytokines in the nasal mucosa of normal and perennial rhinitic subjects. The mast cell as a source of IL-4, IL-5, and IL-6 in human allergic mucosal inflammation. 837 6

Monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), RANTES, and macrophage inflammatory protein (MIP)-1 alpha are chemokines known to activate basophils (MCAF/RANTES) and eosinophils (RANTES/MIP-1 alpha). IL-8 inhibits MCAF-induced histamine release from basophils. We questioned whether a relationship exists between the levels of these chemokines and various inflammatory mediators released from mast cells, eosinophils, and basophils as assessed in nasal secretions obtained from patients during the allergy season and out of season. Samples were assessed for MCAF/MCP-1, RANTES, MIP-1 alpha, IL-8, histamine, tryptase and eosinophil cationic protein (ECP) in three subject groups: subjects with allergic rhinitis (n = 18), atopic subjects without rhinitis (n = 9), and healthy individuals (n = 6). Statistically significant differences were apparent only in the subjects with symptoms as follows. MCAF/MCP-1 increased during the season from 336 +/- 47 pg/ml to 829 +/- 137 pg/ml (p < 0.001), whereas IL-8 decreased from a baseline of 1932 +/- 335 pg/ml to 1070 +/- 202 pg/ml (p < 0.028). The ratio of IL-8 to MCAF/MCP-1 decreased during the symptomatic season from the baseline of 6.66 +/- 1.06 seen during winter to 1.3 +/- 0.22 during ragweed season (p < 0.001). Histamine increased from 6.3 +/- 1.5 to 89 +/- 15.5 ng/ml (p < 0.001), ECP increased from 20.6 +/- 6.4 to 237.1 +/- 50.2 ng/ml (p < 0.001), and tryptase increased from 2.34 +/- 0.6 to 9.7 +/- 2.3 U/ml (p < 0.001). Most samples did not have detectable quantities of MIP-1 alpha or RANTES. We also found a correlation between the level of MCAF/MCP-1 and IL-8 and the level of histamine or IL-8 and ECP. Our results suggest that the chemokines MCAF/MCP-1 and IL-8 may participate in the pathogenesis of allergic rhinitis, contributing to the attraction of the proinflammatory cells and mediator release, which might be very important during the late phase of the allergic reaction. Furthermore, the ratio of certain chemokines, such as MCAF/MCP-1 and IL-8 may reflect the magnitude of the reaction, as does the presence of histamine and ECP.
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PMID:Chemokines in seasonal allergic rhinitis. 856 22

Nasal provocation (NP) in allergic rhinitis patients can elicit a late phase inflammatory response in which interleukins (IL), leukotrienes (LT), and neutrophils have been implicated. Certain antihistamines have been shown to have anti-inflammatory properties. The objective was to determine whether astemizole at 10 mgs/day has any anti-inflammatory characteristics. We clinically evaluated 20 patients with allergic rhinitis and measured nasal IL-8 and LTB4 during NP with increasing doses of grass and ragweed antigen in a double-blind placebo-controlled fashion after a 4-week course of treatment. Clinical symptom scores for sneezing, pruritus, and rhinorrhea were evaluated. Nasal fluid was examined by ELISA and RIA for IL-8 and LTB4 levels along with neutrophil assessment before NP and at 3, 6, and 8 hours. Symptom scores for nasal sneezing, pruritus, rhinorrhea, and nasal LTB4 levels at 6 and 8 hours and IL-8 at 3, 6, and 8 hours were generally lower in astemizole-treated patients compared to those on placebo. Nasal IL-8 levels corresponded to LTB4 levels at diluent and at 6 hours in the placebo group (P = 0.01). The percentage of neutrophils correlated with LTB4 levels at baseline, coefficient = 0.76, P = 0.02 and at 6 hours, coefficient = 0.62, P = 0.035 in the placebo group. This study is the first to demonstrate an effect of astemizole during NP on IL-8 and LTB4 levels with a significant correlation of neutrophil numbers in untreated patients during the nasal late phase response.
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PMID:Late phase response during nasal challenge: effect of astemizole on leukotriene B4 levels. 893 1

Allergic rhinitis involves an early phase, largely mediated through mast cells, and a late phase which involves cellular infiltration and mediator release. In the early phase, mast cells release mediators as a result of antigen cross-linking adjacent immunoglobulin E molecules bound to mast cell surfaces. This results in an accumulation of histamine which gives rise to the characteristic symptoms of rhinitis--sneezing, itching, rhinorrhoea and congestion. The late phase of the allergic response (hours after challenge) involves infiltration of the nasal epithelium by eosinophils, basophils, monocytes and T-lymphocytes, which release leukotrienes, kinins, histamine and a host of other mediators. The most important part of the late-phase response is probably mediated via the production of cytokines (IL-4, IL-5, IL-6, IL-8, GM-CSF and RANTES) by mast cells, TH2 lymphocytes or epithelial cells. The infiltration of tissues by cells normally present only in the blood is brought about by the production of adhesion molecules, such as VCAM-1 and E-selectin, which cause circulating eosinophils, basophils and T-lymphocytes to adhere to endothelial cells before moving through the endothelium into the tissue (diapedesis). Neuronal reflexes also play a role in the allergic response, both by mediating local responses to mediators and possibly playing a part in the activation of T-lymphocytes. The allergic response has also been shown to be less intense in a hot, humid environment, and more marked in a cold, dry environment, possibly due to changes in osmolality of the nasal surface fluid. Similar factors may play a role in the aetiology of non-allergic rhinitis.
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PMID:Pathophysiology of perennial allergic rhinitis. 921 57


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