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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythromycin (EM) and its 14-member macrolide analogues have attracted attention for its effectiveness in a variety of airway diseases, including diffuse panbronchiolitis (DPB), sinobronchial syndrome, and chronic sinusitis. However, its mechanisms of action remain unelucidated. We evaluated the effects of several antibiotics on IL-8 expression by normal and transformed human bronchial epithelial cells, an important source of this potent chemokine involved in cell recruitment into the airways. EM and clarithromycin (CAM) uniquely suppressed mRNA levels as well as the release of IL-8 at the therapeutic and noncytotoxic concentrations (% inhibition of IL-8 protein release: 25.0 +/- 5.67% and 37.5 +/- 8.99%, respectively, at 10(-6) M). The other antimicrobes, including a 16-member macrolide josamycin, showed no effect. Bronchial epithelial cells from very peripheral airways as well as from main bronchi were obtained from patients with chronic airway inflammatory diseases, and EM and CAM inhibited IL-8 release from these cells. Among five patients who underwent bronchoscopy before and after macrolide treatment, four showed decreased levels of IL-8 expression in airway epithelium as assessed by reverse transcription and polymerase chain reaction. Our findings showed these 14-member macrolides had inhibitory effect on IL-8 expression in human bronchial epithelial cells, and this new mode of action may have relevance to their clinical effectiveness in airway diseases.
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PMID:Erythromycin modulates IL-8 expression in normal and inflamed human bronchial epithelial cells. 923 Jul 59

Effects of long-term low-dose macrolide administration were studied in patients with chronic sinusitis. Twelve patients with non-allergic chronic sinusitis were orally given 150 mg roxithromycin once a day without other treatments. The patients underwent computed tomography before and after the treatment, and paranasal sinus aeration was analyzed quantitatively. The number of neutrophils in the nasal smear was semiquantitatively assessed on a grading scale, and the IL-8 concentration in the nasal discharge was measured by enzyme immunoassay. The aeration of all four sinuses significantly improved, and recruited neutrophils and the IL-8 level in the nasal discharge were simultaneously reduced after the treatment. These findings suggest that long-term low-dose roxithromycin administration inhibits the positive feedback mechanism of neutrophil recruitment and IL-8 production by the recruited neutrophils, which is considered to be an essential cause of the prolongation of sinusitis.
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PMID:Effects of long-term low-dose macrolide administration on neutrophil recruitment and IL-8 in the nasal discharge of chronic sinusitis patients. 926 30

Chronic refractory sinusitis is a common feature in patients with primary immunodeficiencies. The efficacy of standard therapeutic strategies is questionable. In an open trial we evaluated the efficacy of azithromycin, N-acetylcysteine and topical intranasal beclomethasone (100 microg twice daily for 6 weeks) in 16 patients with primary immunodeficiencies (median age 13.5 years, range 5-32 years). All patients suffered from chronic sinusitis despite regular immunoglobulin replacement therapy every 3 weeks. Magnetic resonance imaging (MRI) scans were performed before and after 6 weeks of treatment to evaluate morphological changes in the paranasal sinuses. Nasal swabs and washings were taken for microbial analysis and measurement of inflammatory mediators (IL-8, tumour necrosis factor-alpha (TNF-alpha), eosinophilic cationic protein (ECP)) before and post therapy. Inflammatory mediators in nasal secretions were significantly elevated in patients: IL-8 median 2436 pg/ml (range 441-5435 pg/ml), TNF-alpha 37.3 pg/ml (3.75-524 pg/ml) and ECP 33 ng/ml (1.5-250 ng/ml) versus age-matched healthy controls: IL-8 median 212 pg/ml (99-825 pg/ml), TNF-alpha 3.77 pg/ml (2.8-10.2 pg/ml) and ECP 1.5 ng/ml (1.5-14.8 ng/ml) (P < 0.0001). Inflammation of the maxillary sinuses was confirmed by MRI scans in all patients, additionally infection of the ethmoidal and frontal sinuses was recorded in five patients. Bacterial growth appeared in 11 out of 16 cultures. In spite of therapy, no improvement in sinal inflammation visualized by MRI was achieved. Moreover, no significant decrease in pathogens and levels of inflammatory mediators could be detected (IL-8 1141 pg/ml, 426-4556 pg/ml; TNF-alpha 13.9 pg/ml, 4.1-291.6 pg/ml; ECP 32.3 ng/ml, 3.7-58.4 ng/ml). Our results demonstrate that conventional management of sinusitis is of little benefit in patients with chronic refractory sinusitis with an underlying immunodeficiency. More studies are needed to test antibiotic regimens, probably combined with surgical drainage and anti-inflammatory agents.
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PMID:Chronic sinusitis refractory to standard management in patients with humoral immunodeficiencies. 932 24

The mechanism of macrolide therapy in chronic sinusitis patients is unclear. The authors studied the effect of macrolides on interleukin (IL)-8 secretion from cultured human nasal epithelial cells. Epithelial cells harvested from the nasal polyps of patients with chronic sinusitis were primary-cultured, and secreted IL-8 in culture media was measured by enzyme immunoassay. The cells secreted considerable amounts of IL-8 constitutively and in response to lipopolysaccharide. The secretion was significantly inhibited by 10(-5) M of erythromycin, clarithromycin, roxithromycin, and josamycin. 10(-6) M erythromycin still showed the inhibitory effect, whereas the same concentration of josamycin did not. These results indicate that macrolide antibiotics may act as an immunomodulator to reduce IL-8 in inflammatory sites and, at least partially, account for the clinically discrepant effects between 14- and 16-membered ring macrolides in long-term low-dose therapy for chronic sinusitis.
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PMID:Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells. 939 83

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

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.
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PMID:[Clinical features and characteristics of paranasal sinus effusion in allergic sinusitis]. 971 Oct 83

Cytokines are potent biologic factors involved in the regulation of inflammation, immune defense, and wound healing. Recently, growing interest has developed in the role of cytokines in chronic sinusitis and nasal polyposis. In the present study, we investigated the cytokine profile of different types of rhinosinusitis in order to evaluate whether a specific form of rhinosinusitis is associated with the expression of a certain cytokine profile. Sinus mucosa from patients with acute sinusitis (n = 10), chronic sinusitis (n = 7), antrochoanal polyp (n = 10), nasal polyps (n = 8) and controls of turbinate mucosa (n = 7) were sampled. The cytokine protein content (IL-1 beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-13, GM-CSF, interferon-gamma) of tissue homogenates was measured using ELISA technique. In acute sinusitis, the synthesis of proinflammatory cytokines and of the neutrophil chemokine IL-8 and IL-3 appeared to be upregulated. Chronic sinusitis mucosa demonstrated no significantly increased concentrations of the measured cytokines. In bilateral nasal polyposis, but not in antrochoanal polyps, the eosinophil related cytokine IL-5 was strongly upregulated. From these findings, it appears that specific cytokine patterns are found in different forms of sinusitis, and that IL-5 may represent the most important cytokine responsible for tissue eosinophilia in nasal polyposis.
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PMID:Cytokines in nasal polyposis, acute and chronic sinusitis. 988 92

This study aimed to investigate expression of various cytokine mRNAs, including IL-6, IL-8, TGF-beta, IL-4, IL-5, and IFN-gamma in maxillary sinus mucosa of patients with chronic sinusitis. Maxillary sinus mucosae of six patients with chronic sinusitis and turbinate mucosae of six healthy subjects were obtained. We performed RT-PCR and Southern blot to examine gene expression of the cytokines IL-6, IL-8, TGF-beta, IL-4, IL-5, and IFN-gamma in maxillary sinus mucosa and compared the results with cytokine gene expressions in normal turbinate mucosa. IL-6, IL-8, TGF-beta, IL-4, IL-5, and IFN-gamma mRNAs were expressed more frequently in maxillary sinus mucosa from patients with chronic sinusitis than in normal turbinate mucosa. All the maxillary sinus mucosa specimens revealed relatively higher mean density ratio for each cytokine investigated than did normal turbinate mucosa. IL-6, IL-8, TGF-beta, IL-4, IL-5, and IFN-gamma mRNAs were expressed simultaneously in maxillary sinus mucosa of chronic sinusitis. These cytokines may be responsible for recruitment of inflammatory cells and for mucosal thickening in chronic sinusitis, and thus chronicity of the disease.
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PMID:Increased expression of IL-4, IL-5, IFN-gamma, IL-6, IL-8, and TGF-beta mRNAs in maxillary mucosa of patients with chronic sinusitis. 1058 10

Low-dose, long-term macrolide treatment has recently been reported to be very effective in patients with chronic airway diseases. We examined the in vivo and in vitro effects of 14-membered macrolide antibiotics erythromycin (EM) and clarithromycin (CAM) on interleukin (IL)-8 secretion from human nasal epithelial cells. Fifteen patients with chronic sinusitis received macrolide treatment (CAM 400 mg/day) for 1 to 3 months. The number of infiltrated neutrophils and IL-8 concentrations in the nasal discharges of these patients decreased significantly at 1 to 2 months after the treatment. In vitro effects of EM and CAM on IL-8 secretion were examined in nasal epithelial cells cultured at the air-liquid interface. After 14-day culture in the air-liquid interface, macrolide antibiotics were added in medium for 24 h. EM and CAM at concentrations of 10(-4) M did not affect spontaneous secretions or IL-1 beta-induced secretions of IL-8 either apically or basolaterally. When cells were preincubated with 10(-4) M CAM for 7 days, the IL-1 beta-induced secretion of IL-8 decreased significantly. However, no difference was observed between the effects of 10(-4) M CAM and 10(-4) M josamycin, a 16-membered macrolide. These results suggest that macrolide treatment inhibits neutrophil infiltration and IL-8 secretion in nasal epithelium in vivo and that these clinical effects depend on a mechanism other than the direct action of macrolide on nasal epithelial cells.
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PMID:Effects of macrolides on interleukin-8 secretion from human nasal epithelial cells. 1086 34

Macrolides have been used for decades as an important chemotherapeutic agent in the treatment of infectious diseases. In the last 10 years there has also been increasing interest in the interaction between macrolide antibiotics and the immune system. The aim of this review is to focus on the anti-inflammatory action of erythromycin and its derivatives in the treatment of chronic sinusitis and nasal polyps. Systematic clinical investigations have been few and to the author's knowledge there have been no placebo-controlled studies. However there have been, especially from Japan, a number of clinical reports stating that long-term, low-dose macrolide antibiotics are effective in treating chronic sinusitis incurable by surgery or glucocorticosteroid treatment, with an improvement in symptoms varying between 60% and 80% in different studies. In animal studies macrolides have increased mucociliary transport, reduced goblet cell secretion and accelerated apoptosis of neutrophils, all factors that may reduce the symptoms of chronic inflammation. There is also increasing evidence in vitro of the anti-inflammatory effects of macrolides. Several studies have shown macrolides to inhibit interleukin gene expression for IL-6 and IL-8 and also to inhibit the expression of intercellular adhesion molecule essential for the recruitment of inflammatory cells. There is also evidence in vitro, as well as clinical experience, showing that macrolides reduce the virulence and tissue damage caused by chronic bacterial colonization without eradicating the bacteria. The benefit of long-term, low-dose macrolide treatment seems to be that it is, in selected cases, effective when steroids fail. The exact mechanism of action is not known, but it probably involves downregulation of the local host immune response as well as a downgrading of the virulence of the colonizing bacteria. In the future, placebo-controlled studies should be performed to establish the efficacy of macrolides if this treatment is to be accepted as evidence-based medicine.
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PMID:The anti-inflammatory effect of erythromycin and its derivatives, with special reference to nasal polyposis and chronic sinusitis. 1127 May


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