Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The currently available respiratory topical corticosteroids are all effective at reducing the nasal symptoms of itch, sneezing, rhinorrhoea and obstruction associated with allergic rhinitis. The mechanism of action of corticosteroids is related to their anti-inflammatory activities. They have been documented to prevent fluid exudation and reduce the number of circulating inflammatory cells, including lymphocytes, mast cells, basophils, eosinophils, macrophages, and neutrophils. This occurs through multiple mechanisms, e.g. eosinophil infiltration is suppressed by preventing cytokine production, reducing local mechanisms of tissue infiltration, and decreasing eosinophil survival. Furthermore, corticosteroids also reduce preformed and newly-generated mediators (e.g. histamine, tryptase, prostanoids, leukotrienes), and inhibit production of cytokines and chemokines by inflammatory cells (e.g. IL-1 through IL-6, IL-8, RANTES, TNF-alpha, IFN-gamma and GM-CSF). The currently available corticosteroids differ pharmacologically. Fluticasone propionate appears to have the greatest affinity for the glucocorticoid receptor, and binds more quickly and dissociates more slowly from the receptor compared with other corticosteroids, suggesting a more prolonged duration of action. Its increased specificity for respiratory tissue may lead to greater potency with less potential for systemic adverse effects. Fluticasone propionate has been compared with other corticosteroids in animal models for relative topical and systemic potency, and according to these data, it has the most favourable risk-benefit ratio.
 ...
PMID:The pharmacological basis for the treatment of perennial allergic rhinitis and non-allergic rhinitis with topical corticosteroids. 921 61

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.
 ...
PMID:Inflammatory mechanisms in chronic sinusitis. 944 69

Recent studies have suggested that antihistamines, widely used in the treatment of symptoms of patients with allergic rhinitis, may also possess antiinflammatory properties. The mechanisms underlying this property, however, are not clearly understood. We have cultured epithelial cells from nasal biopsy specimens from patients with seasonal allergic rhinitis outside the pollen season and studied the effect of 0 to 10(-3) mol/L fexofenadine, the main active metabolite of terfenadine, on eosinophil-induced changes in electrical resistance (measure of permeability) and release of proinflammatory mediators from these cells. Additionally, we have studied the effect of this drug on eosinophil chemotaxis and adherence to endothelial cells induced by conditioned medium from these human nasal epithelial cell (HNEC) cultures. Incubation of HNEC in the presence of eosinophils treated with opsonized latex beads significantly decreased the electrical resistance of these cultures, an effect that was abrogated by treatment of the cultures with 10(-9) to 10(-3) mol/L fexofenadine. Similarly, incubation of HNEC in the presence of eosinophils treated with latex beads also significantly increased the basal release of the chemokine "regulated upon activation, normal T cell expressed and secreted" (RANTES) (from 96.0 to 613.0 fg/microg cellular protein; p < 0.05), IL-8 (from 42.0 to 198.5 pg/microg cellular protein; p < 0.05), granulocyte-macrophage colony-stimulating factor (GM-CSF) (from 0.54 to 3.4 pg/microg cellular protein; p < 0.05), and soluble intercellular adhesion molecule-1 (sICAM-1) (from 7.8 to 18.4 pg/microg cellular protein; p < 0.05) from HNEC. The eosinophil-induced release of IL-8, GM-CSF, and sICAM-1 from the HNEC was significantly attenuated by treatment with fexofenadine. Analysis of the effects of conditioned medium from HNEC demonstrated that this significantly increased both eosinophil chemotaxis and adherence to endothelial cells. Addition of 10(-6) to 10(-3) mol/L fexofenadine to the conditioned medium significantly attenuated eosinophil chemotaxis and adherence to endothelial cells. These results suggest that fexofenadine may reduce nasal inflammation by modulating the release of proinflammatory mediators and adhesion molecules from HNEC.
 ...
PMID:Effect of fexofenadine on eosinophil-induced changes in epithelial permeability and cytokine release from nasal epithelial cells of patients with seasonal allergic rhinitis. 952 60

Rhinorrhea is a prominent symptom of the common cold. Although increases in vascular permeability and serous cell secretion have been demonstrated in human nasal mucus during active rhinovirus infections, changes in mucin constituents have not been quantified. Nonallergic (n = 48) and asymptomatic allergic rhinitis (n = 32) subjects were inoculated with rhinovirus type hanks before the spring allergy season. Nasal lavages were performed before inoculation (day 0), then daily for 5 days afterward. The subjects were divided into infected and noninfected groups on the basis of evidence of successful rhinovirus infection (nasal shedding of virus or fourfold increases in specific serum antibodies). Concentrations of interleukin (IL)-8, markers of vascular leak (IgG), seromucous cells (lysozyme), and mucoglycoprotein exocytosis [7F10-immunoreactive mucin (7F10-irm) and Alcian blue staining of acidic mucoglycoproteins] were measured in lavage fluids. The infected subgroup had maximal increases in nasal lavage fluid concentrations of IL-8 (sevenfold), IgG (fourfold), total protein (twofold), and gel-phase 7F10-irm (twofold) on day 3. There were no differences between infected allergic and nonallergic subjects. IL-8 and gel-phase 7F10-irm were significantly higher in infected than in noninfected subjects. In addition to promoting plasma exudation, rhinovirus hanks infection increases IL-8 and gel-phase mucin secretion. These processes may contribute to a progression from watery rhinorrhea to mucoid discharge, with mild neutrophilic infiltration during the common cold.
 ...
PMID:Rhinovirus infection induces mucus hypersecretion. 960 41

Plain paranasal sinus radiographs including occipitofrontal and occipitomental views often show abnormal shadows in patients with allergic rhinitis. For that reason, the relationship between chronic sinusitis and allergy has been discussed for many years. Type I allergy is thought to be involved in the sinusitis which is called allergic sinusitis. However, there is not enough information pertaining to this disorder. In order to determine the clinical feature and the characteristics of paranasal sinus effusion in allergic sinusitis, we investigated the differences between 20 patients with allergic sinusitis and 20 with non-allergic chronic sinusitis used as controls. Clinical symptoms (nasal discharge, nasal obstruction, headache, postnasal discharge) and anterior rhinoscopic findings (nasal discharge, nasal edema), clinical examinations (type of x ray maxillary sinus shadow, bacteriology of nasal discharge), and pathological features of the paranasal sinus effusion were examined and compared in the two kind of sinusitis. Pathological findings of the effusion sampled from 14 patients with allergic sinusitis and 15 with non-allergic sinusitis included the number of eosinophils, activated eosinophils and neutrophils, concentrations of interleukin (IL)-1 beta, IL-4, IL-5, IL-8, and concentrations of leukotriene C4/D4/E4 and prostaglandin E2. The incidence and degree of postnasal discharge as a symptom and a nasal finding were lower in allergic sinusitis patients than in the controls. Microorganisms were detected less frequently in the allergic group. The number of eosinophils, activated eosinophils and neutrophils was higher in the paranasal sinus effusion of the patients with allergic sinusitis. The concentrations (ng/mg of protein) of IL-1 beta and IL-8 showed no difference between the two groups, but IL-4, and IL-5 were more prevalent per mg of protein in the effusion of allergic sinusitis patients. These findings suggest that the clinical features of allergic sinusitis include a low incidence and degree of postnasal discharge and a low rate of detection of bacteria, and that the sinus effusion is characterized by the presence of more eosinophils, activated eosinophils, and IL-5 than in those of chronic sinusitis.
 ...
PMID:[Clinical features and characteristics of paranasal sinus effusion in allergic sinusitis]. 971 Oct 83

Nasal polyps are the most common mass lesion of the nasal cavity. Various pathogenetic mechanisms have been proposed. However, the cause is still largely unknown, and treatment methods have not been changed for several hundred years. In order to investigate the role of cytokines in the pathogenesis of nasal polyps, expression of cytokine messenger RNAs (mRNAs) in nasal polyps was investigated. We performed reverse transcriptase-polymerase chain reaction and Southern blot to examine gene expression of the cytokines interleukin (IL)-1 beta, IL-6, IL-8, transforming growth factor (TGF)-beta, IL-4, IL-5, and interferon (IFN)-gamma and compared the results with the gene expressions of these cytokines in normal nasal mucosa. Nasal polyp tissues were obtained from 14 patients undergoing polypectomy for nasal obstruction. Among them, 4 patients suffered from associated perennial allergic rhinitis. The mRNAs of IL-4 and IL-5 (Th2 cytokines) as well as IFN-gamma (Th1 cytokine) were expressed in all of the nasal polyps obtained from the 14 patients, irrespective of the presence or absence of allergy, while 2, 0, and 4 of 6 normal turbinate mucosae expressed IL-4, IL-5, and IFN-gamma mRNAs, respectively. The mRNAs of IL-1 beta, IL-6, IL-8, and TGF-beta were expressed in 6, 1, 2, and 3 of 6 normal turbinate mucosae, respectively, while the mRNAs of these cytokines were expressed in all of the 14 polyp tissues except IL-6 mRNA, which was expressed in 13 nasal polyp tissues. There were no differences in the mean density ratios of each cytokine band on Southern blot between polyp tissues with allergy and those without allergy. These results suggest that many cytokines are produced in nasal polyps, that they may play important roles in the pathogenesis of nasal polyps, and that allergy per se may not play a fundamental role in the pathogenesis of nasal polyps.
 ...
PMID:Cytokine gene expression in nasal polyps. 971 68

Cytokines are potentially active biological peptides that are known to play an important role in several immune responses. Several studies have reported the existence of a variety of cytokines in the nasal mucosa of patients with allergic rhinitis. However, there are few reports on cytokines released into the nasal secretion. In the present study, we investigated the sources, and levels of three key proinflammatory cytokines namely, IL-6, IL-8, and GM-CSF in the nasal secretion, as well the mechanisms of their release, by ELISA and immunohistochemistry. Firstly, we examined the levels of IL-6, IL-8, and GM-CSF in the nasal secretion after in vivo nasal challenge with methacholine (MC), histamine (HI) and allergen (Ag) in patients with nasal allergy to house dust mite (HDMAR). Next, we examined the levels of IL-6, IL-8, and GM-CSF released, in vitro, after Ag challenge of nasal scrapings from patients with HDMAR. Finally, we examined the sources of these cytokines in the nasal mucosa, by immunohistochemistry. After MC challenge in patients with HDMAR, the concentration of IL-6, but not IL-8, and GM-CSF, was significantly greater on the challenged side than on the contralateral side. Ag and HI provocation induced significantly greater levels of IL-6 and IL-8 secretion in patients with HDMAR, on the challenged side than on the contralateral side. GM-CSF was only detected in the nasal secretion after Ag challenge. Immunoreactivity for IL-6 and IL-8 was very similar in that it was predominantly localised to the apical portion of epithelial cells, the superficial lamina propria, gland cells, and migrating cells. The immunoreactivity for GM-CSF varied slightly from that of IL-6 and IL-8: strong immunoreactivity was detected in the basal part of epithelial cells, basement membrane, glandular ducts, and migrating cells. These results suggest that the levels, sources, and mechanisms of release of IL-6, IL-8, and GM-CSF in the nasal secretion of patients with HDMAR do vary, but are important in the manifestation of the allergic reaction.
 ...
PMID:Mechanisms of IL-6, IL-8, and GM-CSF release in nasal secretions of allergic patients after nasal challenge. 992 57

Since its discovery in 1911, histamine has been recognized as a major mediator in allergic reactions and diseases, and today antihistamines remain important agents in the treatment of these conditions. In addition to its known effects on glands, vessels and sensory nerves, recent data have provided further evidence of histamine's proinflammatory actions, which appear to be mediated mainly by H1 receptors. Thus, findings indicate that histamine is a crucial mediator in both the early and late-phase reactions of an allergic response, playing important roles in cytokine release and in the adhesion process. Histamine has been shown to increase the adhesion of leucocytes to the endothelium and to stimulate production of IL-6 and IL-8 by endothelial cells. It also increases TNF alpha-induced IL-6 production and expression of adhesion molecules. These effects can be inhibited by H1 receptor antagonists. First-generation antihistamines, though moderately effective, showed poor selectivity and caused sedation, due to their penetration of the blood-brain barrier, and other troublesome side-effects. Second-generation antihistamines such as ebastine have increased potency due to greater selectivity for histamine receptors, and improved tolerability due to lack of penetration of the blood brain barrier. Recent studies have shown ebastine 10 mg daily to be effective, safe and well tolerated in the treatment of seasonal allergic rhinitis (SAR), with a rapid onset of action, symptom relief comparable to that seen with topical azelastine or oral loratadine 10 mg o.d., cetirizine 10 mg o.d. or terfenadine 60 mg b.i.d., and no significant side-effects. Ebastine therefore offers a new option in the treatment of seasonal allergic rhinitis.
 ...
PMID:Histamine--a major role in allergy? 998 29

Accumulation of eosinophils in the airways is characteristic of allergic rhinitis and asthma. The tissue eosinophilia may involve both recruitment of mature eosinophils and proliferation of their progenitors. This study examines mature eosinophils (nasal and circulating), their circulating progenitors, and a potential role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in stimulating these progenitors. Twelve subjects with a history of seasonal allergic rhinitis and positive skin prick test for birch pollen were studied during four periods: shortly before, in the early and intense phase, at the end, and well after the Swedish birch-pollen season. Nasal mucosal and circulating eosinophils were examined in both nasal brushings and peripheral blood samples. Eosinophil/basophil progenitors were determined by counting colony-forming units in nonadherent mononuclear blood-cell cultures in methylcellulose at 14 days. The nasal mucosal cytokines GM-CSF, interleukin (IL)-1beta, IL-3, IL-5, IL-6, IL-8, and RANTES were analyzed (ELISA) in nasal lavage (NAL) fluids. All patients developed severe symptoms of rhinitis at the height of the season, with increased numbers of eosinophils in the nasal mucosa (P<0.05) and in the circulation (P<0.05). At this time point, the number of circulating progenitors (P<0.05) and the NAL fluid level of GM-CSF (P<0.05) were also increased. In contrast, there was no change in the NAL fluid levels of IL-1beta, IL-3, IL-6, or IL-8. Neither IL-5 nor RANTES could be detected in any of the NAL fluids. At the end of or after the season, there was no increase in nasal eosinophils or circulating eosinophils or progenitors (P>0.05). Ex vivo addition of GM-CSF (10-100 U) increased the number of blood progenitors grown before (P<0.01) and after (P<0.05) the season, compared with during the season. The in vitro GM-CSF responsiveness of progenitors may be related to whether or not these already have been stimulated endogenously by GM-CSF. Taken together, our data thus suggest that GM-CSF may play a role in vivo to increase production of eosinophilic progenitors in allergic airway disease.
 ...
PMID:Circulating eosinophil/basophil progenitors and nasal mucosal cytokines in seasonal allergic rhinitis. 1032 56

The objectives of this study were to measure interleukins 5 and 8 (IL-5 and IL-8) in relation to eosinophils and neutrophils, in nasal lavage fluids from 60 school children with allergic rhinitis, and to determine the influence of treatment with a topical steroid (budesonide) on the levels of the two cytokines. Highly sensitive enzyme immunoassays were used to analyze IL-5 and IL-8. IL-5 levels and relative eosinophil counts in nasal lavage fluid increased significantly in patients with allergic rhinitis during the pollen season, compared with values obtained before the start of the season, and decreased significantly after treatment with budesonide. By contrast, no significant changes in IL-8 or neutrophils were found during the pollen season, nor did they decrease following treatment. In the untreated patients, IL-5 levels correlated significantly with eosinophil counts but not with neutrophil counts, whereas IL-8 levels correlated with neutrophil counts but not with eosinophil counts. After budesonide treatment, the correlation between IL-8 and neutrophils remained, and a correlation between IL-8 and eosinophils emerged. These findings support the concepts that IL-5 has a key role in regulating eosinophils and that IL-8 is important for the regulation of neutrophils. Whereas IL-5 and relative eosinophil counts are profoundly affected by topical steroid treatment, IL-8 and neutrophils are not demonstrably affected by such treatment. It is possible that neutrophils, through the release of IL-8, could be chemotactic for eosinophils in steroid-treated patients.
 ...
PMID:Interleukin-5 and interleukin-8 in relation to eosinophils and neutrophils in nasal fluids from school children with seasonal allergic rhinitis. 1056 58


<< Previous 1 2 3 4 5 6 7 8 Next >>