interleukin-8 and Rhinitis--Allergic--Perennial

Airway inflammation with eosinophils is now reported to occur not only in asthma but in other airway diseases such as cough variant asthma, chronic cough, atopic cough, episodic symptoms without asthma, allergic rhinitis, and COPD. Although the prevalence of eosinophilic bronchitis (EB) is less than in asthma, the causes, mechanisms and treatment of EB in these conditions appears to be similar to asthma where allergen induced IL-5 secretion and symptoms are readily responsive to inhaled corticosteroids. The prognosis of EB without asthma is not known but it may be a precursor for asthma and, if so, recognition of this syndrome may permit effective treatment and reduction in the rising prevalence of asthma. Induced sputum analysis allows recognition of EB in clinical practice. The place of the asthma treatment paradigm with early and sustained corticosteroid treatment needs to be defined in EB without asthma. Airway wall remodelling can occur in rhinitis, COPD, and cough variant asthma with EB. The mechanisms and long term implications of this complication in EB without asthma need to be clarified.

Topics: Asthma; Bronchitis; Chronic Disease; Cough; Eosinophilia; Humans; Interleukin-5; Interleukin-8; Pulmonary Disease, Chronic Obstructive; Rhinitis, Allergic, Perennial

To study the mechanism of action and the therapeutic efficacy of treating patients with perennial allergic rhinitis by Qumin Tongbi Nasal Spraying Agent (QTNSA).. One hundred and three patients with perennial allergic rhinitis were randomly assigned to two groups. Of them, 57 patients in the treatment group were treated with QTNSA and 46 patients in the control group were treated with Veconase. Seven days were taken as one therapeutic course, two courses in total. The therapeutic efficacy and the serum levels of interleukin-4 (IL-4), IL-8, immunoglobulin E (IgE) and nasal airway resistance (NAR), symptoms and signs integrals before and after treatment were observed in the two groups.. There was no statistical significance between the treatment group and the control group in the markedly effective rate (61.40% vs. 63. 04%) and the total effective rate (87.72% vs. 89.13%). After treatment symptoms and signs integrals of the two groups were significantly improved when compared with before treatment (P < 0.01). There was no significant difference between the two groups after treatment (P > 0.05). The serum levels of IL-4, IL-8, IgE, and NAR were significantly higher in the two groups than those of the normal group. They significantly decreased after treatment in the two groups, showing statistical difference (P < 0.01). There was no statistical difference between the treatment group and the control group (P > 0.05).. QTNSA could effectively treat perennial allergic rhinitis. It could obviously lower serum levels of IL-4, IL-8, IgE, and NAR in patients with perennial allergic rhinitis.

Topics: Adolescent; Adult; Drugs, Chinese Herbal; Female; Humans; Immunoglobulin E; Interleukin-4; Interleukin-8; Male; Middle Aged; Nasal Sprays; Phytotherapy; Rhinitis, Allergic, Perennial; Young Adult

There is evidence that adenosine plays a role in the pathogenesis of asthma and rhinitis; however, it is currently unclear whether adenosine receptors are useful therapeutic targets in the treatment of allergic airway diseases.. The study evaluated the efficacy of intranasal treatment with an adenosine A(2A) receptor agonist/adenosine A(3) receptor antagonist (50 micro g), administered twice daily for 7 days, to reduce nasal symptoms and release of inflammatory mediators following intranasal allergen challenge in patients with allergic rhinitis (AR). The compound was compared with twice-daily treatment with intranasal fluticasone proprionate nasal spray (FPANS) for 7 days.. A randomized, double-blind, double-dummy, placebo-controlled, three-way balanced, incomplete block, crossover study was conducted on 48 males with verified AR. Following intranasal challenge with either an extract from the house dust mite (HDM), Dermatophagoides pteronyssinus, rye grass or cat dander, nasal responses and the concentrations of albumin, tryptase, myeloperoxidase, eosinophilic cationic protein, epithelial neutrophil-activating protein-78 (ENA-78), IL-5 and IL-8 in nasal secretions were measured and treatment groups were compared.. Drug improved nasal blockage but had no significant effect on rhinorrhoea, number of sneezes or peak nasal inspiratory flow measurements when compared with placebo. Drug reduced tryptase release after EAR but did not significantly reduce the levels of other mediators.. A novel agonist/antagonist of adenosine A(2A) and A(3) receptors appears to have limited clinical benefit in both the early-phase and the late-phase response to intranasal allergen challenge. However, reduction of some pro-inflammatory mediators suggests that comparable, more selective compounds may have additional benefits meriting further investigation.

Topics: Adenosine A2 Receptor Antagonists; Adenosine A3 Receptor Antagonists; Administration, Intranasal; Adolescent; Adult; Allergens; Androstadienes; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents, Non-Steroidal; Betamethasone; Biomarkers; Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Fluticasone; Humans; Interleukin-5; Interleukin-8; Male; Middle Aged; Nasal Lavage Fluid; Nasal Provocation Tests; Placebos; Purinergic P1 Receptor Antagonists; Purines; Rhinitis, Allergic, Perennial; Tetrazoles; Time Factors; Treatment Failure; Tryptases

Cetirizine has been demonstrated able of reducing nasal inflammatory infiltration in children with allergic rhinitis and cytokine production in in vitro studies. The aim of this double-blind, placebo-controlled, and randomized study was to evaluate cytokine pattern and inflammatory cells in children with perennial allergic rhinitis, before and after treatment with cetirizine or placebo. Twenty children with perennial allergic rhinitis were evaluated, 13 males and 7 females (mean age 13.4 years). Inflammatory cells and cytokines were evaluated by scraping and nasal lavage, before and after 2-weeks administration of cetirizine or placebo. IL4 and IL8 were measured by immunoassay and inflammatory cells were counted by conventional staining. Cetirizine treatment induced a significant decrease of IL4 (p<0.01) and IL8 levels (p=0.01). A significant reduction of the inflammatory cells was detected in actively-treated children, both concerning neutrophils and eosinophils (p<0.01). Moreover, cetirizine significantly reduced nasal obstruction score (p=0.007). This study shows the cetirizine effectiveness in exerting anti-inflammatory activity by modulating cytokine pattern and by reducing inflammatory infiltration in children with perennial allergic rhinitis.

Topics: Adolescent; Animals; Cetirizine; Child; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Eosinophils; Female; Histamine H1 Antagonists, Non-Sedating; Humans; Interleukin-4; Interleukin-8; Male; Nasal Lavage Fluid; Nasal Mucosa; Nasal Obstruction; Neutrophils; Pollen; Prospective Studies; Pyroglyphidae; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Treatment Outcome

In our previous study, we found a new mixed formula of Chinese herbs containing Shin-yi-san + Xiao-qing-long-tang + Xiang-sha-liu-jun-zi-tang (9 + 3 + 3 g divided in three doses/day) was beneficial to the patients with perennial allergic rhinitis (AR) via complicated immunomodulatory effects on both mononuclear cells (MNC) and polymorphonuclear neutrophils (PMN). In the present study, we further determined the effects of nasal fluid from AR patients on the functions of human PMN before and after treatment with the mixed formula. We found the nasal discharge, but not serum, from AR group with high serum IgE (H-IgE, serum IgE >200 KIU/l) before treatment exerted many stimulating effects on normal PMN including delayed apoptosis, enhanced production of soluble intercellular adhesion molecule 1 (sICAM-1), interleukin 8 (IL-8) and prostaglandin E2 (PGE2), increased phagocytosis, and augmented cyclooxygenase 2 (COX-2) mRNA expression of PMN. However, these stimulating effects of nasal fluid on PMN were not found in low IgE group (L-IgE, serum IgE <200 KIU/l). These PMN-enhancing effects of H-IgE nasal fluid were abolished after 3-month treatment with the mixed Chinese herb formula. In conclusion, our results suggest that the new mixed herb formula treatment suppressed nasal mucosa inflammation by normalizing stimulatory effects of allergic nasal discharge of patients with H-IgE allergic rhinitis.

Topics: Adolescent; Adult; Apoptosis; Cells, Cultured; Culture Media, Conditioned; Cyclooxygenase 2; Dinoprostone; Drugs, Chinese Herbal; Female; Humans; Immunoglobulin E; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Isoenzymes; Leukotriene C4; Male; Membrane Proteins; Mucus; Nasal Mucosa; Neutrophils; Phagocytosis; Prostaglandin-Endoperoxide Synthases; Rhinitis, Allergic, Perennial; RNA, Messenger; Time Factors

Ozone may play a significant role in the exacerbation of airway disease in asthmatics, either by priming the airway mucosa such that cellular responses to allergen are enhanced or by exerting an intrinsic effect on airway inflammation. Previous investigations of nonasthmatic subjects revealed that ozone induces both nasal and bronchial inflammation, suggesting that nasal responses to ozone may be used as a surrogate marker for the effect of this pollutant on bronchial mucosal inflammation. In this study, the effect of exposure to 0.4 ppm ozone on nasal inflammation in 11 allergic asthmatics sensitive to Dermatophygoides farinae was examined. This study was designed such that the effect of ozone exposure on the late-phase reaction to allergen was emphasized, using eosinophil influx and changes in eosinophil cationic protein as principal endpoints. By employing a "split-nose" design, in which allergen was applied to only one side of the nose while saline was applied to the contralateral side, both the effect of ozone on nasal inflammation due to allergen challenge as well as its direct action on non-allergen-challenged nasal tissues was examined. The results reported herein indicate that ozone exposure has both a priming effect on allergen-induced responses as well as an intrinsic inflammatory action in the nasal airways of perennially allergic asthmatics.

Topics: Adolescent; Adult; Albumins; Allergens; alpha 1-Antitrypsin; Animals; Asthma; Bronchial Provocation Tests; Double-Blind Method; Eosinophils; Female; Humans; Inflammation; Interleukin-8; Leukocyte Count; Male; Mites; Nasal Lavage Fluid; Nasal Mucosa; Ozone; Rhinitis, Allergic, Perennial

Changes in the level of serum neutrophil chemotactic activity (S-NCA) were investigated in 20 subjects with allergic rhinitis, with or without asthma, undergoing clinically effective hyposensitization to house dust mite with Pharmalgen Dermatophagoides pteronyssinus. Two control groups were studied: 28 subjects with allergic rhinitis, with or without asthma, receiving placebo injections for 1 yr in a double-blind controlled trial with Pharmalgen D. pteronyssinus (from whom the actively treated group in this study were recruited), and eight non-atopic asymptomatic controls. S-NCA and serum IgE specific to D. pteronyssinus were measured in the subjects before, during (3-6 months) and 12 months after treatment, and once in the non-atopic controls. The mean S-NCA was significantly higher (0.01 greater than P greater than 0.001) in subjects before treatment (mean +/- s.e. = 63.8 +/- 3.6 arbitrary units of migration (AUM] compared with the non-atopic controls (48.5 +/- 3.7 AUM), but had fallen to normal levels after 6 months (46.8 +/- 4.0 AUM) and 12 months treatment (45.2 +/- 3.8 AUM). The levels of S-NCA in the placebo treated group were significantly higher than normal at the start of treatment (69.2 +/- 4.1) and remained raised throughout the 12 months treatment. In the actively treated group, the level of S-NCA had fallen in 18 out of 19 subjects after 12 months immunotherapy, and was unaltered in one. Mean levels of D. pteronyssinus IgE rose during the first 6 months and declined to initial levels by the end of the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Animals; Chemotactic Factors; Desensitization, Immunologic; Double-Blind Method; Dust; Female; Humans; Immunoglobulin E; Immunotherapy; Injections; Interleukin-8; Male; Mites; Rhinitis, Allergic, Perennial; Time Factors

Asian dust storms (ADS) contain various airborne particles that may augment airway inflammation by increasing the level of interleukin-8. The objective of the study was to investigate the association of exposure to an ADS with worsening of symptoms of adult asthma and the effect of ADS particles on interleukin-8 transcriptional activity.. The subjects were 112 patients with mild to moderate asthma who recorded scores for their daily upper and lower respiratory tract symptoms and measured morning peak expiratory flow (PEF) from March to May 2011. Interleukin-8 transcriptional activity was assessed in THP-G8 cells that were exposed to airborne particles collected during days of ADS exposure.. Of the 112 patients, 31 had comorbid allergic rhinitis (AR) and/or chronic sinusitis (CS), and had worsened scores for upper respiratory tract symptoms on ADS days compared to non-ADS days. Scores for lower respiratory tract symptoms during ADS days were higher than non-ADS days in all patients. Three patients also had unscheduled hospital visits for exacerbation of asthma on ADS days. However, there was no significant difference in daily morning PEF between ADS and non-ADS days. Airborne particles collected on ADS days induced interleukin-8 transcriptional activity in THP-G8 cells compared to the original soil of the ADS.. Exposure to an ADS aggravates upper and lower tract respiratory symptoms in patients with adult asthma. ADS airborne particles may increase airway inflammation through enhancement of interleukin-8 transcriptional activity.

Topics: Aged; Air Pollutants; Asthma; Dust; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Japan; Luciferases; Male; Middle Aged; Particulate Matter; Peak Expiratory Flow Rate; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Sinusitis; Wind

Th17 cells and IL-17A play a role in the development and progression of allergic diseases. We analyzed the IL-17A levels in sputum supernatants (Ss), nasal wash (NW) and plasma (P) from Healthy Controls (HC) and children with Asthma/Rhinitis. We tested the expression of IL-17A, RORγ(t) and FOXP3 in peripheral blood T-lymphocytes from intermittent and mild-moderate asthma. The effect of Budesonide and Formoterol was tested "in vitro" on IL-17A, RORγ(t) and FOXP3 expression in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis patients, and on nasal and bronchial epithelial cells stimulated with NW and Ss from mild-moderate asthma/persistent rhinitis. Further, the effect of 12 weeks of treatment with Budesonide and Formoterol was tested "in vivo" in T-lymphocytes from mild-moderate asthma/persistent rhinitis patients. IL-17A was increased in Ss, NW and P from children with mild-moderate asthma compared with intermittent and HC. In cultured T-lymphocytes IL-17A and RORγ(t) expression were higher in mild-moderate asthma/persistent rhinitis than in mild-moderate asthma/intermittent rhinitis, while FOXP3 was reduced. Budesonide with Formoterol reduced IL-17A and RORγ(t), while increased FOXP3 in cultured T-lymphocytes from mild-moderate asthma/persistent rhinitis, and reduced the IL-8 release mediated by IL-17A present in NW and Ss from mild-moderate asthma/persistent rhinitis in nasal and bronchial epithelial cells. Finally, Budesonide with Formoterol reduced IL-17A levels in P and Ss, CD4(+)IL-17A(+)T-cells, in naïve children with mild-moderate asthma/persistent rhinitis after 12 weeks of treatment. Th17 mediated immunity may be involved in the airway disease of children with allergic asthma and allergic rhinitis. Budesonide with Formoterol might be a useful tool for its therapeutic control.

Topics: Administration, Inhalation; Adolescent; Adrenergic beta-2 Receptor Agonists; Anti-Asthmatic Agents; Asthma; Budesonide; Case-Control Studies; Cells, Cultured; Child; Ethanolamines; Female; Forkhead Transcription Factors; Formoterol Fumarate; Humans; Interleukin-17; Interleukin-8; Male; Nasal Lavage Fluid; Nuclear Receptor Subfamily 1, Group F, Member 3; Rhinitis, Allergic, Perennial; Sputum; Th17 Cells

Kaempferol (KP) is a major compound of Naju Jjok (Polygonum tinctorium Lour.). The effect of KP on allergic rhinitis (AR) has not been elucidated. Here, we report the effects and mechanisms of KP on new and predominant mediators of AR using an eosinophil cell line, Eol-1 and an ovalbumin (OVA)-induced AR mouse model. KP significantly inhibited the production of interleukin (IL)-32 and IL-8 and activation of caspase-1 in Eol-1 cells. Allergic symptoms and predominant mediators (IgE and histamine) in the KP-administered group were significantly lower than in the AR group. The levels of interferon-γ were enhanced while the levels of IL-4 were reduced in the KP group. KP significantly reduced the levels of IL-32 and thymic stromal lymphopoietin (TSLP) compared with the AR mice. KP reduced the levels of inflammation-related proteins. In the KP-administered groups, the infiltrations of eosinophils and mast cells increased by OVA were decreased. In addition, KP significantly reduced caspase-1 activity in nasal mucosa tissue of AR mice. Our findings indicate that KP has an anti-allergic effect through the regulation of the production of IL-32 and TSLP and caspase-1 activity in allergic diseases including AR.

Topics: Animals; Anti-Allergic Agents; Caspase 1; Cell Line; Cytokines; Disease Models, Animal; Enzyme Activation; Eosinophils; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Histamine; Humans; Immunoglobulin E; Interleukin-4; Interleukin-8; Interleukins; Kaempferols; Mast Cells; Mice; Mice, Inbred BALB C; Organ Size; Ovalbumin; Rhinitis, Allergic; Rhinitis, Allergic, Perennial; Spleen; Thymic Stromal Lymphopoietin

Recent investigations suggest that neutrophils may play an important role in the late-phase allergen-induced inflammation in allergic airway diseases. The aim of this study was to evaluate neutrophil chemotaxis, phagocytic activity, and reactive oxygen species (ROS) production in patients with allergic rhinitis and asthma challenged with inhaled Dermatophagoides pteronyssinus. Eighteen patients with allergic rhinitis and 14 with allergic asthma, all sensitized to D. pteronyssinus, as well as 15 healthy individuals underwent bronchial challenge with D. pteronyssinus. Peripheral blood collection and neutrophil isolation were performed 24 h before as well as 7 and 24 h after bronchial challenge. Neutrophils chemotaxis, phagocytic activity, and ROS production were analyzed by flow cytometer. Neutrophil chemotaxis and ROS production were increased, while phagocytic activity was decreased 24 h before challenge in patient groups compared with healthy individuals. After challenge, neutrophil chemotaxis and phagocytic activity increased after 7 and 24 h, when ROS production, only after 24 h. Bronchial allergen challenge had no influence for neutrophils activity in healthy subjects. Activated chemotaxis, phagocytic activity, and ROS production of peripheral blood neutrophils after challenge with D. pteronyssinus reflect an enhanced systemic inflammation in allergic rhinitis and asthma patients with induced late-phase airway inflammation.

Topics: Adult; Animals; Asthma; Chemotaxis, Leukocyte; Dermatophagoides pteronyssinus; Female; Humans; Interleukin-8; Male; Neutrophils; Phagocytosis; Reactive Oxygen Species; Respiratory Hypersensitivity; Rhinitis, Allergic, Perennial

We sought to investigate the type and kinetics of late-phase nasal inflammatory response after nasal challenge with occupational allergens. Participants were 10 subjects experiencing work-related rhinitis symptoms who underwent specific inhalation challenge and tested positive for occupational rhinitis. During challenge, we monitored changes in inflammatory cells, eosinophil cationic protein, myeloperoxidase, and interleukin-8 in nasal lavage samples. The challenge with the active agent induced a significant increase in the percentage of eosinophils at 30 minutes as compared with prechallenge values (P = 0.04). A significant increase in eosinophil cationic protein levels after challenge with the control (P = 0.01) and active agent (P = 0.02) was observed in the late phase after challenge. No significant changes in nasal levels of neutrophils, myeloperoxidase, and interleukin-8 were observed on both control and active challenge days. Our results suggest a predominant nasal eosinophilic inflammatory response after occupational allergen challenge.

Topics: Administration, Inhalation; Analysis of Variance; Enzyme-Linked Immunosorbent Assay; Eosinophil Cationic Protein; Female; Humans; Inflammation Mediators; Interleukin-8; Lactose; Male; Neutrophils; Occupational Exposure; Peroxidase; Respiratory Hypersensitivity; Rhinitis, Allergic, Perennial; Skin Tests; Statistics, Nonparametric; Therapeutic Irrigation

The mechanism of action involved in how Dermatophagoides pteronyssinus (Der p) 1 initiates the nasal allergic cascade is poorly understood.. We detected proinflammatory cytokine production (GM-CSF, TNF-α, IL-1β, IL-6, and IL-8) and associated signal molecules in primarily cultured nasal epithelial cells (NECs) from patients with allergic rhinitis (AR) after Der p1 stimulation, using ELISA, RT-PCR, and Western blot. We also evaluated the importance of protease-activated receptors (PAR)/phosphatidylinositol 3 kinase (PI3K)/NFκB signaling pathways in IL-6 and IL-8 production using glucocorticoids and specific inhibitors, LY294002 and PDTC.. We observed significantly elevated IL-6 and IL-8 production (both gene and protein) in NECs after Der p1 stimulation, and demonstrated that the expressions of PAR2, pAkt, and pp65 were upregulated after Der p1 stimulation, which were associated with IL-6 and IL-8 production in NECs.. These findings demonstrate that the PAR/PI3K/NFκB signaling pathway is involved in the induction of IL-6 and IL-8 in Der-p1-stimulated NECs from AR patients, and may have potential implications for the prevention and treatment of AR and asthma.

Topics: Adult; Antigens, Dermatophagoides; Arthropod Proteins; Asthma; Cells, Cultured; Cysteine Endopeptidases; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Nasal Mucosa; NF-kappa B; Phosphatidylinositol 3-Kinases; Receptor, PAR-1; Receptor, PAR-2; Rhinitis, Allergic, Perennial; RNA, Messenger; Signal Transduction; Young Adult

Among proteases, metalloproteases are implicated in tissue remodeling, as shown in numerous diseases including allergy. ADAMs (A Disintegrin And Metalloprotease) metalloproteases are implicated in physiologic processes such as cytokine and growth factor shedding, cell migration, adhesion, or repulsion. Our aim was to measure ADAM-12 expression in airway epithelium and to define its role during the allergic response. To raise this question, we analyzed the ADAM-12 expression ex vivo after allergen exposure in patients with allergic rhinitis and in vitro in cultured primary human airway epithelial cells (AEC). Clones of BEAS-2B cells transfected with the full-length form of ADAM-12 were generated to study the consequences of ADAM-12 up-regulation on AEC function. After allergen challenge, a strong increase of ADAM-12 expression was observed in airway epithelium from patients with allergic rhinitis but not from control subjects. In contrast with the other HB-epidermal growth factor sheddases, ADAM-10 and -17, TNF-alpha in vitro increased the expression of ADAM-12 by AEC, an effect amplified by IL-4 and IL-13. Up-regulation of ADAM-12 in AEC increased the expression of alpha3 and alpha4 integrins and to the modulation of cell migration on fibronectin but not on collagen. Moreover, overexpression of ADAM-12 in BEAS-2B enhanced the secretion of CXCL1 and CXCL8 and their capacity to recruit neutrophils. CD47 was strongly decreased by ADAM-12 overexpression, a process associated with a reduced adhesion of neutrophils. These effects were mainly dependent on epidermal growth factor receptor activation. In summary, ADAM-12 is produced during allergic reaction by AEC and might increase neutrophil recruitment within airway mucosa.

Topics: ADAM Proteins; ADAM12 Protein; Allergens; Bronchi; CD47 Antigen; Cell Adhesion; Cells, Cultured; Chemokine CXCL1; Chemotaxis, Leukocyte; Epithelial Cells; ErbB Receptors; Gene Expression Regulation; Humans; Integrins; Interleukin-8; Membrane Proteins; Neutrophils; Recombinant Fusion Proteins; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Transfection; Tumor Necrosis Factor-alpha

To survey the effects of TNF-alpha and IL-8 in the pathogenesis of allergic rhinitis.. The serum levels of TNF-alpha and IL-8 in 102 cases of seasonal or non-seasonal allergic rhinitis were detected pre and post specific immunotherapy (SIT), and the results were statistically analyzed.. The levels of TNF-alpha and IL-8 in experiment group were significant higher than that in the health control. And the levels of TNF-alpha and IL-8 significantly decreased post SIT in the experiment group.. TNF-alpha and IL-8 play important roles in the pathogenesis of allergic rhinitis.

Topics: Adolescent; Adult; Humans; Interleukin-8; Middle Aged; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Tumor Necrosis Factor-alpha; Young Adult

Allergic rhinitis is associated with Th2-dependent inflammation. Nasal obstruction is the most typical symptom in children with mite allergy.. The aim of this study was to evaluate the possible relationships among nasal symptoms, allergic inflammation, including inflammatory cells and cytokine pattern, and nasal airflow in children with persistent allergic rhinitis because of mite sensitization.. Twenty children (13 males and seven females, mean age 13.4 +/- 1.6 years) with persistent rhinitis because of mite allergy were evaluated. All of them had moderate-severe grade of nasal obstruction. Total symptom score (TSS), rhinomanometry, nasal lavage, and nasal scraping were obtained in all subjects. Inflammatory cells were counted by conventional staining; interleukin (IL)-5, and IL-8 were measured by immunoassay on fluids recovered from nasal lavage.. Eosinophils were significantly associated with TSS (R = 74.4%, P = 0.0002), with IL-5 (R = 90.6%, P < 0.0001) and with nasal flow (R = -69%, P = 0.0007), but not with IL-8 (R = 0.1%, P = 0.995). Eosinophil levels were shown to independently predict nasal flow (P < 0.001), with flow decreasing linearly for increasing eosinophils, together with a significant effect of neutrophils (P = 0.016, linear increase in flow) and a borderline effect of IL-8 (P = 0.063, linear increase in flow).. This study demonstrates the close association between IL-5 concentration and eosinophil infiltration. In addition, there is clear evidence concerning the relationship between eosinophil infiltration and nasal airflow. Thus, nasal eosinophils can be regarded as the most important predictor of upper airway function. These findings constitute first evidence of the relationship between nasal airflow impairment and Th2-related eosinophilic inflammation in children with persistent allergic rhinitis because of mite sensitization.

Topics: Adolescent; Child; Cohort Studies; Cytokines; Eosinophils; Female; Humans; Inflammation; Interleukin-5; Interleukin-8; Male; Nasal Obstruction; Neutrophils; Prospective Studies; Pyroglyphidae; Rhinitis, Allergic, Perennial; Th2 Cells

Recent studies have shown that airborne latex allergens cause allergic rhinitis and bronchial asthma.. The aim of this study was to investigate the association between the development of rhinitis reactions during workplace-related inhalative challenge tests and nasal allergic inflammation.. Thirty-two health care workers (HCWs) with suspected respiratory hypersensitivity to latex allergens underwent an inhalative workplace-related challenge test with powdered latex gloves. Nasal lavage fluid (NALF) and nasal brushing (NAB) material were collected before and after exposure (30 min, 2, 6 and 24 h) to determine mediator and cellular composition. In addition, lung function parameters and nasal flow were recorded. Furthermore, six healthy controls underwent nasal brushing and nasal lavage without latex allergen challenge at the same time intervals.. Twenty-six HCWs showed acute rhinitis by contact to airborne latex allergen exposure and 10 of them had an additional asthma response. Only in responders, significantly increased eosinophil levels were found 6 h (P < 0.00001) and 24 h (P < 0.0005) post-challenge when compared with the prechallenge values. The ECP levels measured 2, 6 and 24 h post-challenge in the responder group were significantly elevated when compared with the prechallenge values as well as with the non-responders (6 h: P < 0.05, 24 h: P < 0.00001 afterwards). Only in some concentrated NALF samples of responders collected 30 min post-challenge (seven out of 15) tryptase concentration above the detection limit were found. The NO derivative concentrations in NALF were significantly increased 6 h post-challenge compared with the prechallenge values (P < 0.05) and were significantly higher in responders than in non-responders and in controls (P < 0.002). IL-5 levels increased post-challenge in the responder group with a pronounced effect 6 h after challenge (P < 0.001). Overall, a variety of parameters was significantly correlated (e.g. ECP with NO derivatives, r = 0.792 P < 0.002).. Our data demonstrate for the first time that nasal and bronchial hyperreactivity to airborne latex allergens are associated with an increase of eosinophils and mediators (e.g. ECP, NO derivatives, IL-5, tryptase) in nasal mucosa. The combined use of NAB (for cells) and NALF (for mediators) appears to be a useful model to monitor nasal inflammation during workplace-related challenge tests.

Topics: Administration, Inhalation; Adult; Albumins; Blood Proteins; Bronchial Provocation Tests; Cell Differentiation; Chymases; Eosinophil Granule Proteins; Epithelial Cells; Female; Health Personnel; Humans; Intercellular Adhesion Molecule-1; Interleukin-5; Interleukin-8; Latex Hypersensitivity; Leukocyte Count; Male; Middle Aged; Nasal Lavage Fluid; Nasal Mucosa; Nitric Oxide; Occupational Diseases; Proteins; Rhinitis, Allergic, Perennial; Ribonucleases; Serine Endopeptidases; Tryptases

IL-6, IL-8 and GM-CSF regulate inflammatory cell infiltration and survival at sites of inflammation. IL-1, TNF-alpha, IL-6, IL-8 and GM-CSF have been reported to be released from cultured nasal epithelial cells (CNEC). Here, focusing on IL-1 and TNF-alpha as key cytokines, we examined whether these two cytokines could regulate the release of IL-6, IL-8 and GM-CSF from CNEC. CNEC were treated with antibodies to IL-1 alpha and TNF-alpha at various doses for a period of 48 hrs. The levels of IL-6, IL-8 and GM-CSF in the culture supernatants were then estimated by ELISA. Treatment of CNEC with antibodies to IL-1 alpha and TNF-alpha inhibited the release of IL-6, IL-8 and GM-CSF from them in a dose-dependent manner. The inhibition of IL-6 and GM-CSF release was significantly greater after treatment of the CNEC with the antibodies to IL-1 alpha. Furthermore CNEC expressed IL-1 receptors and TNF receptors. These results suggest that the epithelial cell-derived IL-1 alpha and TNF-alpha can regulate the release of other cytokines like IL-6, IL-8 and GM-CSF in an autocrine manner.

Topics: Adult; Autocrine Communication; Cells, Cultured; Epithelial Cells; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Nasal Mucosa; Receptors, Interleukin-1; Receptors, Tumor Necrosis Factor; Rhinitis, Allergic, Perennial; Tumor Necrosis Factor-alpha

Laser surgery of the inferior turbinates has become a popular surgical treatment for patients with allergic rhinitis, particularly for those who have persistent nasal obstruction and do not respond well to pharmacological therapy. The aim of this study was to investigate the effects of the laser surgery on local cytokine gene expression at the mucosal surface in relation to the improvement of nasal symptoms.. A prospective analysis of 25 patients with allergic rhinitis caused by the house dust mite who underwent laser surgery twice with a 1-month interval on an outpatient basis. Fifteen healthy volunteers served as normal control subjects.. Improvement of the nasal symptoms was evaluated on a graded scale. Nasal mucosal cells were obtained by brushing from the inferior turbinate at each visit. The expression of messenger RNA (mRNA) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, RANTES (regulated on activation, normal T-cell expressed and secreted), and eotaxin was semiquantitatively analyzed by reverse transcription-polymerase chain reaction (RT-PCR).. Two months after treatment, the nasal symptom scores significantly decreased from baseline. The decrease was most apparent in nasal obstruction. RT-PCR analysis revealed that a significant decrease in IL-8 and RANTES expression (P < .001 and P = .012, respectively) was observed after successive laser treatment, and the reduction in these cytokines was significantly correlated. On the other hand, mRNA expression of GM-CSF, IL-6, and eotaxin remained unchanged.. This study provided evidence that the expression of local inflammatory cytokines can be attenuated in part by CO2 laser treatment, which may be closely related to the clinical effectiveness of this procedure.

Topics: Adult; Analysis of Variance; Chemokine CCL11; Chemokine CCL5; Chemokines, CC; Cytokines; Female; Gene Expression Regulation; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-6; Interleukin-8; Male; Nasal Obstruction; Prospective Studies; Rhinitis, Allergic, Perennial; RNA, Messenger

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.

Topics: Adolescent; Adult; Alcian Blue; Coloring Agents; Exocytosis; Glycoproteins; Humans; Immunoglobulin G; Interleukin-8; Middle Aged; Mucus; Muramidase; Nasal Mucosa; Picornaviridae Infections; Rhinitis, Allergic, Perennial; Rhinovirus; Therapeutic Irrigation

Leukotriene B4 (LTB4), a potent chemokinetic mediator for neutrophils, is enhanced by interleukin-8 (IL-8) and may play a key role in the inflammatory response of asthma.. The aim of the present study was to investigate whether zileuton, a 5-lipoxygenase antagonist known to inhibit LTB4 production and recruitment of eosinophils/neutrophils in bronchoalveolar fluid, could affect the production of LTB4 and IL-8 by allergen-stimulated peripheral blood mononuclear cells in vitro from patients with asthma and/or allergic rhinitis.. Peripheral blood mononuclear cells were isolated using Ficoll-Hypaque density gradient from 14 subjects (2 with asthma, 11 with asthma and allergic rhinitis, and 1 with allergic rhinitis) and were stimulated by selected allergens (grass, tree, mite, and mold) in the absence or presence of 1 and 10 microM of zileuton. Supernatants were collected and assayed for LTB4 and IL-8 levels using RIA and ELISA, respectively.. Levels of LTB4 were significantly elevated in peripheral blood mononuclear cells stimulated with mold, grass, and tree compared with the unstimulated control group (P<.05). Levels of IL-8 were significantly elevated in all allergen-stimulated peripheral blood mononuclear cells, except mold, compared with the unstimulated control group (P<.05). Zileuton significantly reduced production of LTB4 by mold and tree-stimulated peripheral blood mononuclear cells. By contrast, no effect of zileuton on IL-8 production was observed in allergen-stimulated peripheral blood mononuclear cells.. The zileuton-induced attenuation of LTB4 production by allergen-stimulated peripheral blood mononuclear cells from patients with asthma and/or allergic rhinitis occurs independently from the allergen-stimulated IL-8 production.

Topics: Adult; Aged; Allergens; Asthma; Female; Humans; Hydroxyurea; Interleukin-8; Leukocytes, Mononuclear; Leukotriene B4; Lipoxygenase Inhibitors; Male; Middle Aged; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

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.

Topics: Animals; Enzyme-Linked Immunosorbent Assay; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Immunohistochemistry; Interleukin-6; Interleukin-8; Mites; Mucus; Nasal Mucosa; Nasal Provocation Tests; Rhinitis, Allergic, Perennial; Sensitivity and Specificity

Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and primed eosinophils. In allergic rhinitis, allergen exposure triggers leucocyte recruitment.. We evaluated in this study IL-8 secretion and the neutrophil chemotactic activity in nasal lavages collected after a nasal allergen challenge. Moreover, the participation of IL-8 in the neutrophil chemotactic activity was quantified.. Four healthy subjects and 19 patients with allergic rhinitis were exposed to a nasal allergen challenge. As a control, saline challenge was performed in four patients with allergic rhinitis. Concentration of IL-8 was measured by ELISA in nasal lavages collected before and after challenge. Neutrophil chemotactic assay was developed using a 48-well chemotaxis microassembly.. After allergen challenge, the healthy subjects, the four patients receiving saline and one patient exposed to allergen did not respond; seven patients presented a single early reaction and 11 patients a dual response. For healthy subjects and the four patients exposed to saline, the level of IL-8 did not increase after challenge in comparison with that at baseline. After allergen challenge, two peaks of IL-8 release were observed for patients with allergic rhinitis during the early (30 min to 1 h 30 min) and the late periods (3 h 30 min to 9 h 30 min), however the difference was not significant for the early period. During the late period, a significant increase in IL-8 concentrations was detected for the patients developing a dual response, whereas the difference was not significant for those presenting only an early reaction. The neutrophil chemotactic activity of nasal lavages from patients with allergic rhinitis collected during the early and the late reactions (17 +/- 2.1 and 23.3 +/- 2.8 neutrophils per high power field (hpf), respectively) was significantly higher than the activity of lavage fluid collected at baseline (9.2 +/- 1.8 neutrophils per hpf). Nevertheless, the addition of a neutralizing anti-IL-8 antibody inhibited weakly the chemotactic activity of lavage fluid from rhinitic patients collected during the early or the late periods (18 and 11% of inhibition) (P = NS).. These data show that allergen challenge increased significantly the secretion of IL-8 for the patients with allergic rhinitis. However, neutralization of IL-8 in nasal lavages by a specific antibody revealed that the role of this chemokine in granulocyte infiltrate was limited, suggesting that IL-8 acts in connection with other chemotactic factors in this recruitment.

Topics: Adult; Allergens; Animals; Case-Control Studies; Chemotactic Factors; Chemotaxis, Leukocyte; Female; Humans; In Vitro Techniques; Interleukin-8; Male; Mites; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Neutralization Tests; Neutrophils; Pollen; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

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.

Topics: Administration, Topical; Adult; Androstadienes; Anti-Inflammatory Agents; Cell Count; Cells, Cultured; Depression, Chemical; Eosinophils; Epithelium; Female; Fluticasone; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-6; Interleukin-8; Male; Mast Cells; Nasal Mucosa; Rhinitis, Allergic, Perennial

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.

Topics: Adult; Female; Humans; Immunohistochemistry; Interleukin-4; Interleukin-5; Interleukin-6; Interleukin-8; Interleukins; Male; Mast Cells; Nasal Mucosa; Rhinitis, Allergic, Perennial; T-Lymphocytes