interleukin-8 and montelukast

This meta-analysis aimed to compare the efficacy of montelukast (MKST) combined with budesonide (BUD) and BUD alone in the treatment of pulmonary inflammation and pulmonary function in children with cough variant asthma (CVA). Five electronic databases were searched for studies about MKST+BUD therapy and BUD alone therapy on inflammation and pulmonary function in CVA children from inception to November 23, 2021. Twenty-two articles were included. The results showed that, compared with BUD alone, the combination treatment could achieve better improvement of pulmonary function and lower levels of inflammation (MKST+BUD group: FEV1: SMD = 2.77, 95% CI: 2.07, 3.46; FVC: SMD = 2.54, 95% CI: 1.82, 3.27; PEF: SMD = 2.27, 95% CI: 1.79, 2.75; IgE: SMD = -7.95, 95% CI: -9.66, -6.25; TNF-α: SMD = -4.67, 95% CI: -6.04, -3.31; IL-8: SMD = -8.18, 95% CI: -11.46, -4.90; BUD alone group: FEV1: SMD = 1.83, 95% CI: 1.34, 2.31; FVC: SMD = 1.39, 95% CI: 0.93, 1.84; PEF: SMD = 1.51, 95% CI: 1.13, 1.89; IgE: SMD = -4.93, 95% CI: -6.14, -3.72; TNF-α: SMD = -2.78, 95% CI: -3.76, -1.80; IL-8: SMD = -4.94, 95% CI: -7.10, -2.79). To conclude, compared with BUD alone, MKST+BUD therapy was found to be more effective in improving pulmonary function and reducing inflammation in CVA children. Key Words: Montelukast, Budesonide, Cough variant asthma, Children, Pulmonary function, Inflammatory markers, Meta-analysis.

Topics: Asthma; Budesonide; Child; Cough; Humans; Immunoglobulin E; Inflammation; Interleukin-8; Tumor Necrosis Factor-alpha

Few studies have compared treatment strategies in patients with asthma poorly controlled on low dose inhaled corticosteroids, and little is known about the effects of different treatments on airway inflammation. In this double-blind, placebo-controlled, parallel group study, we compared the effects of salmeterol plus fluticasone propionate (FP) (Seretide; SFC) and FP plus montelukast (FP/M) on sputum inflammatory markers, airway responsiveness, lung function, and symptoms in adult asthmatics.. Sixty-six subjects were randomised to SFC or FP/M for 12 weeks. The primary outcome was changes in neutrophil, eosinophil, macrophage, lymphocyte, and epithelial cell levels in induced sputum. Additional outcomes included the change in other sputum markers of airway inflammation, airway responsiveness, symptom control, and lung function.. Both treatments had no significant effect on induced sputum inflammatory cells, although there was a trend for a reduction in sputum eosinophils. Both treatments significantly improved airway responsiveness, whereas SFC generally led to greater improvements in symptom control and lung function than FP/M. FP/M led to significantly greater reductions in sputum cysteinyl leukotrienes than SFC (treatment ratio 1.80; 95% CI 1.09, 2.94).. Both treatments led to similar control of eosinophilic airway inflammation, although PEF and symptom control were better with SFC. STUDY NUMBER: SAM40030 (SOLTA).

Topics: Acetates; Adrenergic beta-Agonists; Adult; Albuterol; Androstadienes; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Cyclopropanes; Cysteine; Double-Blind Method; Drug Combinations; Female; Fluticasone; Fluticasone-Salmeterol Drug Combination; Forced Expiratory Volume; Histamine; Humans; Interleukin-8; Leukotriene Antagonists; Leukotrienes; Lung; Male; Quinolines; Spirometry; Sputum; Sulfides; Time Factors; Treatment Outcome; United Kingdom

In cystic fibrosis (CF), the inflammatory process contributes to progressive lung tissue damage. Cysteinyl leukotrienes have been found in the sputum of patients with CF at high concentrations sufficient to cause potent biological effects.. To evaluate the effect of anti-inflammatory treatment with montelukast sodium in patients with CF.. Twenty-six patients aged 6 to 18 years were recruited to this 20-week, randomized, double-blind, placebo-controlled, crossover trial. Patients received montelukast or placebo for 8 weeks in addition to their regular CF treatment. Before and after treatment, findings from spirometry, whole-body plethysmography, and the clinical wheezing and cough scales were evaluated. At the same time, serum and sputum samples were obtained for the measurement of eosinophil cationic protein, interleukin 10 (IL-10), IL-8, and myeloperoxidase levels.. Twenty-three patients completed the study. Compared with placebo use, montelukast treatment significantly improved forced expiratory volume in I second, peak expiratory flow, and forced expiratory flow between 25% and 75% and significantly decreased cough and wheezing scale scores (P < .001 for all). There were no significant changes in vital capacity, thoracic gas volume, airway resistance, and residual volume after treatment. Compared with placebo use, montelukast treatment decreased serum and sputum levels of eosinophil cationic protein and IL-8, decreased sputum levels of myeloperoxidase, and increased serum and sputum levels of IL-10 (P < .001 for all).. Montelukast may have measurable anti-inflammatory properties in patients with CF.

Topics: Acetates; Adolescent; Airway Resistance; Anti-Asthmatic Agents; Child; Cough; Cross-Over Studies; Cyclopropanes; Cystic Fibrosis; Double-Blind Method; Eosinophil Cationic Protein; Female; Forced Expiratory Volume; Humans; Interleukin-10; Interleukin-8; Male; Peroxidase; Quinolines; Respiratory Sounds; Sputum; Sulfides; Treatment Outcome

Immune-mediated inflammation contributes to progressive pulmonary damage in cystic fibrosis (CF). Sputum cysteinyl leukotriene levels, eosinophil cationic protein (ECP), and interleukin-8 (IL-8) are significantly related to disease severity.. The aim of this study was to evaluate the anti-inflammatory and clinical effects of the cysteinyl leukotriene receptor antagonist montelukast in children with CF.. A double-blind, randomized, crossover design was used. Patients received montelukast (6 to < or = 14 years, 5 mg; > 14 years, 10 mg) or placebo as a once-daily tablet for 21 days and then, after a washout period of at least 4 weeks, crossed over to receive the alternative treatment. Blood and native nasal fluid were taken on days 1 and 21 of each treatment block, and WBC count, ECP, and IL-8 were analyzed using a chemiluminescent immunometric assay.. Sixteen CF patients (10 boys, 6 girls; age, 5 to 18 years, median 9.5 years) completed the trial. There was a significant (P < or = 0.02) reduction of serum ECP (median reduction: montelukast 7.7 microg/L vs placebo 0.15 microg/L) and eosinophils (P < or = 0.027; median reduction: montelukast 85/microL vs placebo 0/microL). There was no significant change in nasal ECP, IL-8, or serum IL-8 after a 21-day course of montelukast. Clinical symptom scores did not change significantly.. Montelukast reduces eosinophilic inflammation in CF patients. Multicenter trials providing more patients to create more data to prove the hypothesis that montelukast is an effective tool to cut down disease severity in CF patients are needed.

Topics: Acetates; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Blood Proteins; Child; Cross-Over Studies; Cyclopropanes; Cystic Fibrosis; Double-Blind Method; Eosinophil Granule Proteins; Eosinophilia; Humans; Inflammation; Interleukin-8; Leukocyte Count; Leukotriene Antagonists; Membrane Proteins; Pilot Projects; Quinolines; Receptors, Leukotriene; Respiratory Function Tests; Ribonucleases; Sulfides; Treatment Outcome

Survival after lung transplantation is hampered by chronic lung allograft dysfunction (CLAD). Persistently elevated BAL-neutrophilia is observed in some patients despite treatment with azithromycin, which may be induced by IL-1α. Our aim is to establish an in vitro model, assess mechanistic pathways and test different therapeutic strategies of IL-1α-induced release of IL-8 by human bronchial epithelial cells. Bronchial epithelial cells (16HBE) were stimulated with IL-1α with or without azithromycin or dexamethasone. IL-8 protein was analyzed in cell supernatant. Different MAP kinases (p38, JNK, ERK

Topics: Acetates; Acetylcysteine; Aminopyridines; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Azithromycin; Benzamides; Bronchi; Cell Line; Cyclopropanes; Dapsone; Dexamethasone; Dose-Response Relationship, Drug; Epithelial Cells; Fluoroquinolones; Humans; Interleukin-1alpha; Interleukin-8; MAP Kinase Signaling System; Moxifloxacin; Neutrophils; Phosphorylation; Pyridones; Quinolines; Sulfides; Theophylline; Treatment Outcome

Microparticles (MPs) are membrane fragments that may play a role in the pathogenesis of chronic respiratory diseases. We aimed to investigate whether human monocytes/macrophage-derived MPs could induce a pro-inflammatory phenotype in human bronchial smooth muscle cells (BSMC) and the effect of montelukast in this setting. Experimental methods included isolation of human monocytes/macrophages and generation of monocyte-derived MPs, RT-PCR analysis of gene expression, immunoenzymatic determination of pro-inflammatory factor release, bioluminescent assay of intracellular cAMP levels and electromobility shift assay analysis of NF-κB nuclear translocation. Stimulation of human BSMC with monocyte-derived MPs induced a pro-inflammatory switch in human BSMC by inducing gene expression (COX-2 and IL-8), protein release in the supernatant (PGE2 and IL-8), and heterologous β2-adrenoceptor desensitization. The latter effect was most likely related to autocrine PGE2 since pre-treatment with COX inhibitors restored the ability of salbutamol to induce cAMP synthesis in desensitized cells. Challenge with MPs induced nuclear translocation of NF-κB and selective NF-κB inhibition decreased MP-induced cytokine release in the supernatant. Montelukast treatment prevented IL-8 release and heterologous β2-adrenoceptor desensitization in human BSMC exposed to monocyte-derived MPs by blocking NF-κB nuclear translocation. These findings provide evidence on the role of human monocyte-derived MPs in the airway smooth muscle phenotype switch as a novel potential mechanism in the progression of chronic respiratory diseases and on the protective effects by montelukast in this setting.

Topics: Acetates; Active Transport, Cell Nucleus; Anti-Asthmatic Agents; Bronchi; Cell Line; Cell-Derived Microparticles; Cells, Cultured; Cyclooxygenase 2; Cyclopropanes; Gene Expression Regulation; Humans; Interleukin-8; Monocytes; Myocytes, Smooth Muscle; NF-kappa B; Quinolines; Receptors, Adrenergic, beta; Signal Transduction; Sulfides

Clinical manifestations suggest that air pollution may induce deterioration of respiratory health. Some air pollutants, including sulfite, may play a role in the exacerbation of asthma. Sulfites are formed at bronchial mucosa from inhaled sulfur dioxide. It has been previously reported that sodium sulfite (Na(2)SO(3)) has pro-inflammatory properties and enhances neutrophil adhesion to A549 cells. Interleukin-8 (IL-8) plays a critical role in attracting inflammatory cells and is an excellent marker of pulmonary cell activation. To date, there have not been any reports on the effect of asthma drugs on the suppression of IL-8 production induced by sulfite in A549 cells or the involvement of specific signal transduction pathways. Thus, our study assessed the effects of salmeterol, fluticasone, and montelukast on human epithelial lung cell inflammation as well as the inhibitors in different signal transduction pathways.. A549 human lung epithelial cells were cultured under the following conditions: (1) treated with sodium sulfite (0, 100, 500, 1000, 2500 uM) for 16 hours; (2) cultured for 1 hour in the presence of SB203580, PD98059, SP600125, or wedeloactone, then co-incubated with sodium sulfite for another 16 hours; (3) cultured for 4 hours in the presence of salmeterol, fluticasone, or montelukast, then stimulated with sodium sulfite at a concentration of 1000 uM for 16 hours. We collected the supernatants from the above conditions and performed enzyme-linked immunosorbent assay (ELISA) to measure the IL-8 concentration.. IL-8 production increased after treatment with sodium sulfite at 1000 to 2500 uM (p

Topics: Acetates; Air Pollutants; Albuterol; Androstadienes; Anti-Asthmatic Agents; Cell Line; Cell Survival; Cyclopropanes; Dose-Response Relationship, Drug; Epithelial Cells; Fluticasone; Humans; Inflammation; Interleukin-8; Lung; Quinolines; Salmeterol Xinafoate; Signal Transduction; Sulfides; Sulfites

Montelukast is a potent cysteinyl leukotriene-1 receptor antagonist possessing some anti-inflammatory effects although the molecular mechanism of these anti-inflammatory effects is unknown. In this study, we aimed to investigate the effect of montelukast on nuclear factor (NF)-kappaB-associated histone acetylation activity in phorbol myristate acetate (PMA)-differentiated U937 cells.. We examined the inhibitory effects of montelukast on TNF-alpha-induced IL-8 production in PMA-differentiated U-937 cells. U-937 cells were exposed to PMA (50 ng/mL) for 48 h to allow differentiation to macrophages. Macrophages were then exposed to TNF-alpha (10 ng/mL) in the presence or absence of montelukast (0.01-10 microm) for 24 h. After this time, the concentration of IL-8 in the culture supernatant was measured by sandwich-type ELISA kit. The effect of signalling pathways on TNF-alpha-induced IL-8 release was examined pharmacologically using selective NF-kappaB/IKK2 (AS602868, 3 microm), (PD98059, 10 microm) and p38 mitogen activated protein kinase (MAPK) (SB203580, 1 microm) inhibitors. NF-kappaB DNA binding activity was measured by a DNA-binding ELISA-based assay. NF-kappaB-p65-associated histone acetyltransferase (HAT) activity was measured by immunoprecipitation linked to commercial fluorescent HAT.. TNF-alpha-induced IL-8 release was suppressed by an NF-kappaB inhibitor but not by MEK or p38 MAPK inhibitors. Montelukast induced a concentration-dependent inhibition of TNF-alpha-induced IL-8 release and mRNA expression that reached a plateau at 0.1 microm without affecting cell viability. Montelukast did not affect NF-kappaB p65 activation as measured by DNA binding but suppressed NF-kappaB p65-associated HAT activity.. Montelukast inhibits TNF-alpha-stimulated IL-8 expression through changes in NF-kappaB p65-associated HAT activity. Drugs targeting these enzymes may enhance the anti-inflammatory actions of montelukast.

Topics: Acetates; Cyclopropanes; Histone Acetyltransferases; Humans; Interleukin-8; Leukotriene Antagonists; Macrophages; NF-kappa B; Quinolines; Signal Transduction; Sulfides; Tumor Necrosis Factor-alpha; U937 Cells

Lipoxin A(4) (LXA(4)) and its stable analogs downregulate chemokine secretion in polarized epithelia. This anti-inflammatory effect has been suggested to be mediated by the LXA(4) receptor (LXA(4)R), a G protein-coupled receptor. To determine whether LXA(4)R is expressed on the apical, basolateral, or both poles of intestinal epithelia, an NH(2)-terminal c-myc epitope tag was added to the human LXA(4)R cDNA and recombinant retroviruses were used to transduce polarized epithelial cells. In polarized T84 intestinal epithelial cells, c-myc-LXA(4)R was preferentially expressed on the basolateral surface as indicated by cell surface-selective biotinylation and confocal microscopy. Furthermore, expression of c-myc-LXA(4)R and a truncation mutant lacking the cytoplasmic terminus was primarily confined to the lateral subdomain. We also observed that the expression of myc-LXA(4) conferred enhanced downregulation of IL-8 expression in response to LXA(4) analog and that blockade of the CysLT1 receptor by montelukast did not prevent this response to LXA(4) analog. Thus LXA(4) generated in or near the paracellular space via neutrophil-epithelial interactions can rapidly act on epithelial LXA(4)R to downregulate epithelial promotion of intestinal inflammation.

Topics: Acetates; Anti-Inflammatory Agents, Non-Steroidal; Cyclopropanes; Genetic Vectors; Humans; Hydroxyeicosatetraenoic Acids; Interleukin-8; Intestinal Mucosa; Leukotriene Antagonists; Lipoxins; Membrane Proteins; Quinolines; Receptors, Cell Surface; Receptors, Formyl Peptide; Receptors, Leukotriene; Receptors, Lipoxin; Retroviridae; Sulfides; Tissue Distribution; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

The cysteinyl leukotrienes (cysLTs) and the peptide hormone endothelin (ET)-1 are potent bronchoconstrictor substances, and these mediators are also claimed to be implicated in the development of eosinophilic airway inflammation. In the present study, we have investigated the effect of the cysLT1 receptor antagonist montelukaston the development of an eosinophilic airway inflammation 24 h after intratracheal Sephadex (SDX) provocation in rats. Furthermore, the effect of montelukast treatment on the generation of ET-1 and other pro-inflammatory mediators has been studied. The inflammatory response was significantly reduced in the animals receiving SDX + montelukast compared to animals receiving solely SDX, as evaluated by a decrease in bronchoalveolar lavage fluid total cell count (10.3 +/- 1.2 vs. 18.5 +/- 1.8 x 10(4) ml(-1), P<0.001), number of eosinophils (299.7 +/- 43.8 vs. 577.6 +/- 46.6 x 10(2) ml(-1), P<0.001), and lymphocytes (116.8 +/- 20 vs. 222.0 +/- 34.8 x 10(2) ml(-1), P<0.05), as well as the degree of tissue inflammation (P<0.05). Montelukast also inhibited the increase in the concentration of the pro-inflammatory mediators ET-1 (28.5 +/- 75 vs. 40.9 +/- 7.3 x pg ml(-1), P<0.05) and interferon (IFN)-gamma (4.3 +/- 2.2 vs. 15.6+/-8.7 x pg ml(-1), P<0.05), but not tumor necrosis factor-gamma or interleukin-8. In summary, treatment with the cysLT1 receptor antagonist montelukast reduced the inflammatory response during development of an eosinophilic airway inflammation, possibly by inhibiting the release of pro-inflammatory mediators like ET-1 and IFN-gamma.

Topics: Acetates; Animals; Bronchoalveolar Lavage Fluid; Cell Count; Cyclopropanes; Endothelin-1; Eosinophils; Interferon-gamma; Interleukin-8; Leukotriene Antagonists; Lung; Male; Quinolines; Rats; Rats, Wistar; Sulfides; Tumor Necrosis Factor-alpha