Inflammation In Allergic Rhinitis Research Articles

Plasma Paraoxonase Activity and Oxidative Stress and Their Relationship to Disease Severity in Children with Allergic Rhinitis

Oxidative stress may play a role in the pathophysiology of several diseases including allergic rhinitis (AR). In children with AR an antioxidant enzyme paraoxonase (PON1) has not been previously investigated. The aim of this study was to investigate plasma PON1 activity and plasma total oxidant status (TOS), which are in the form of plasma reactive oxidants, and their association with severity of disease in house-mite-sensitive children with AR. This study included 66 children with persistent AR and 40 healthy controls aged between 7 and 12 years old. Plasma PON1, TOS, and total serum immunoglobulin E (IgE) were measured. The nasal symptom scores and body mass index were evaluated at the time of blood collection. Mean serum PON1 levels were significantly lower and, TOS levels were higher in the patient group than in the control group (p ≤ 0.001 and p ≤ 0.002, respectively). A significant negative correlation was observed between serum levels of PON1 and nasal symptom scores. However, serum levels of TOS were correlated with nasal symptom scores positively. There were no correlations between levels of total IgE and levels of PON1 and TOS levels. Plasma PON1 and TOS levels may serve as predictors of disease severity in children with AR and both of them appear to be attractive candidates for modulating inflammation in AR.

Antidepressant Drug, Desipramine, Alleviates Allergic Rhinitis by Regulating Treg and Th 17 Cells

Allergic rhinitis (AR) is characterized by IgE-mediated immediate hypersensitivity and usually progresses to chronic nasal inflammation, with depression as one of its comorbidities. The importance of treating the depression in AR patients has been increasingly recognized. Desipramine is a representative of tricyclic-antidepressant agents. In the present study we investigate whether desipramine has therapeutic effects on AR inflammation. BALB/C mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by repeated challenge with OVA intranasally. Desipramine was administered orally to treat the mice. The nasal symptoms (sneezing, nasal scratching etc.) of AR were evaluated to determine the severity of AR. Cytokines in the nasal lavage fluid (NALF), including interferon-gamma (IFN-gamma), interleukin 4 (IL-4) and serum OVA-specific immunoglobulin E (IgE) antibody were measured by ELISA. The regulatory T cells (Treg) and T helper cells 17 (Th17) were quantified by flow cytometric analysis. As a result, the repeated oral administration of desipramine attenuated the nasal symptoms (sneezing and nasal rubbing) in AR mice. Desipramine also suppressed the serum OVA-specific IgE and IL-4 levels, but had no effect on IFN-gamma level. Moreover, desipramine treatment up regulated CD4+CD25+Foxp3+ Treg cells, which were found down-regulated in established AR mice. Meanwhile, desipramine administration attenuated CD4+IL-17+ Th17 cells, which were significantly increased in AR mice. These results suggest that the antidepressant drug, desipramine, also has anti-allergic action, which was possibly achieved by reducing allergen-specific IgE and Th2 cytokine production and maintaining a balance between Treg and Th17 cells. Thus, this study provide the first evidence that desipramine may be utilized to treat allergic diseases, especially for those allergic patients with depression or depression patients with allergy.

Effect of KOB03, a polyherbal medicine, on ovalbumin-induced allergic rhinitis in guinea pigs

BackgroundKOB03 is a polyherbal medicine that originated from the oriental prescription for the treatment of chronic allergic diseases such as rhinitis and asthma. This study aims to evaluate the effect of KOB03 on ovalbumin (OVA)-induced allergic rhinitis (AR) in guinea pigs.MethodsHartley guinea pigs were sensitized to OVA by intraperitoneal injection on days 0, 7, and 14 and challenged with intranasal exposure to OVA three times for 7 days after the last sensitization. KOB03 at doses of 200 and 500 mg/kg were orally administrated to guinea pigs once daily during challenge. The serum levels of histamine, OVA-specific immunoglobulin (Ig) E, eosinophil cationic protein (ECP) and cytokines (TNF-α, IL-4 and IFN-γ) in OVA sensitization/challenge-induced AR guinea pigs were measured. We also observed histological changes in nasal tissues of AR guinea pigs by staining with H&E, Periodic acid-Schiff, and toluidine blue.ResultsThe administration of KOB03 at a dose of 500 mg/kg significantly decreased the serum levels of histamine (P = 0.001), OVA-specific IgE (P = 0.0017), ECP (P = 0.008), and TNF-α (P = 0.0003) in OVA-sensitized/challenged guinea pigs compared with controls. KOB03 significantly decreased the serum levels of a Th2 cytokine, IL-4 (P = 0.017), while significantly increasing the levels of a Th1 cytokine, IFN-γ (P = 0.0006) in OVA-sensitized/challenged guinea pigs compared with controls. In addition, KOB03 suppressed the epithelial destruction, goblet cell hyperplasia and eosinophilic infiltration into nasal mucosa associated with AR.ConclusionKOB03 may regulate allergic inflammation in AR by inhibiting nasal damage, the release of allergic mediators and modulating the balance of Th1/Th2 cytokines.

Blocking interleukin-17 attenuates enhanced inflammation by staphylococcal enterotoxin B in murine allergic rhinitis model

Conclusion: The results of this study suggest that staphylococcal enterotoxin B (SEB) enhances inflammation in allergic rhinitis (AR) and interleukin (IL)-17 may play a significant role in regulation of the inflammatory process induced by SEB. Objectives: Exposure to SEB is associated with severe symptoms in AR patients. However, how SEB influences the inflammatory process in AR has not been elucidated so far. The aim of this study was to identify the role of SEB and IL-17 in AR. Methods: BALB/c and IL-17-deficient mice were divided into three groups: control, OVA, and SEB groups. The control group was challenged with phosphate-buffered saline, the AR group was challenged with ovalbumin (OVA), and the SEB group was treated with SEB before OVA challenge. Nasal symptoms, eosinophil infiltration, serum total and OVA-specific immunoglobulin E levels, and cytokine levels including IL-1β, IL-4, IL-6, and interferon (IFN)-γ in splenocyte culture were compared between the groups. Results: The SEB group produced significantly greater amounts of cytokines such as IL-1β, IL-4, IL-6, and IFN-γ than the OVA group in wild-type mice. However, these enhanced inflammatory responses in the SEB group compared with the OVA group were not observed in IL-17-deficient mice.

Peripheral Blood Neutrophil Activity During Dermatophagoides pteronyssinus-Induced Late-Phase Airway Inflammation in Patients with Allergic Rhinitis and Asthma

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.

Eosinophilic Inflammation in Allergic Rhinitis and Nasal Polyposis

On histopathological examination, nasal polyps and nasal mucosa in allergic rhinitis show different forms of pseudostratified respiratory epithelium, whereas the dominant characteristic of lamina propria is an eosinophilic infiltration. The aim of this study was to compare interleukin (IL)-5 and eosinophilic cationic protein (ECP) levels in the nasal fluid of 42 patients: 12 with allergic rhinitis and nasal septal deviation, 17 non-atopic patients with nasal polyposis, and 13 atopic nasal polyp patients were enrolled in this cross-sectional study. Nasal secretion samples were collected a few days before surgery. The levels of IL-5 were measured using flow cytometry and the ECP using a commercial ELISA kit. In addition, we counted eosinophils in hematoxylin-and-eosin-stained sections of all nasal polyp and all nasal mucosa samples taken from the inferior nasal turbinates during septoplasty. A significantly higher concentration of IL-5 was found in the nasal fluid of atopic patients with nasal polyposis than in non-atopic nasal polyp patients (p=0.025) and patients with allergic rhinitis (p=0.05). ECP was higher in atopic nasal polyp patients than in patients with allergic rhinitis (p<0.0001) and than in non-atopic nasal polyp patients (p<0.0001). Polyp eosinophils were higher in atopic' than in non-atopic patients (p<0.0001) and higher than in the mucosa of patients with allergic rhinitis (p<0.0001). These however had significantly more mucosal eosinophils than was found in the polyps of non-atopic patients' (p=0.025). ECP levels in nasal fluid and eosinophil counts in tissue specimens correlated well in all three groups of patients. Our study has shown that atopic nasal polyp patients have a higher level of eosinophilic inflammation than non-atopic patients with nasal polyps and patients with allergic rhinitis.

IL‐32 up‐regulation is associated with inflammatory cytokine production in allergic rhinitis

IL-32 is a described pro-inflammatory cytokine produced by T lymphocytes, natural killer cells, monocytes, and epithelial cells. However, the specific mechanism of IL-32 on allergic rhinitis (AR) has not been elucidated. Here, we report a significant increase of IL-32 protein and mRNA in the nasal mucosa of AR patients. In addition, in nasal mucosa tissue from AR patients, the level of IL-32 production correlated with inflammation, IL-1β, IL-18, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In an AR animal model, IL-32 significantly increased IgE and inflammatory cytokine levels. IL-32 expression was induced by recombinant human GM-CSF via activation of caspase-1 in eosinophils. In addition, depletion of IL-32 prevents the production of inflammatory cytokines in eosinophils. In conclusion, IL-32 is an important cytokine involved in the inflammation of AR. The regulation of IL-32 expression may form the basis of a new strategy for the treatment of AR.

Early phase resolution of mucosal eosinophilic inflammation in allergic rhinitis

BackgroundIt is widely assumed that apoptosis of eosinophils is a central component of resolution of allergic airway disease. However, this has not been demonstrated in human allergic airways in vivo. Based on animal in vivo observations we hypothesised that steroid-induced resolution of human airway eosinophilic inflammation involves inhibition of CCL5 (RANTES), a CC-chemokine regulating eosinophil and lymphocyte traffic, and elimination of eosinophils without evident occurrence of apoptotic eosinophils in the diseased tissue.ObjectiveTo determine mucosal eosinophilia, apoptotic eosinophils, general cell apoptosis and cell proliferation, and expression of CCL5 and CCL11 (eotaxin) in human allergic airway tissues in vivo at resolution of established symptomatic eosinophilic inflammation.MethodsTwenty-one patients with intermittent (birch and/or grass) allergic rhinitis received daily nasal allergen challenges for two seven days' periods separated by more than two weeks washout. Five days into these "artificial pollen seasons", nasal treatment with budesonide was instituted and continued for six days in a double blinded, randomized, placebo-controlled, and crossover design. This report is a parallel group comparison of nasal biopsy histochemistry data obtained on the final day of the second treatment period.ResultsTreatments were instituted when clinical rhinitis symptoms had been established. Compared to placebo, budesonide reduced tissue eosinophilia, and subepithelial more than epithelial eosinophilia. Steroid treatment also attenuated tissue expression of CCL5, but CCL11 was not reduced. General tissue cell apoptosis and epithelial cell proliferation were reduced by budesonide. However, apoptotic eosinophils were not detected in any biopsies, irrespective of treatment.ConclusionsInhibition of CCL5-dependent recruitment of cells to diseased airway tissue, and reduced cell proliferation, reduced general cell apoptosis, but not increased eosinophil apoptosis, are involved in early phase steroid-induced resolution of human allergic rhinitis.

Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis

BackgroundThe CC-chemokine receptor-3 (CCR3) has emerged as a target molecule for pharmacological intervention in allergic inflammation.ObjectiveTo examine whether a dual CCR3 and H1-receptor antagonist (AZD3778) affects allergic inflammation and symptoms in allergic rhinitis.MethodsPatients with seasonal allergic rhinitis were subjected to three seven days' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Symptoms and nasal peak inspiratory flow (PIF) were monitored in the morning, ten minutes post challenge, and in the evening. Nasal lavages were carried out at the end of each challenge series and α2-macroglobulin, ECP, and tryptase were monitored as indices of allergic inflammation.ResultsPlasma levels of AZD3778 were stable throughout the treatment series. AZD3778 and the antihistamine (loratadine) reduced rhinitis symptoms recorded ten minutes post challenge during this period. AZD3778, but not the anti-histamine, also improved nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening nasal symptoms from the last five days of the allergen challenge series showed statistically significant reductions for AZD3778, but not for loratadine. ECP was reduced by AZD3778, but not by loratadine.ConclusionsAZD3778 exerts anti-eosinophil and symptom-reducing effects in allergic rhinitis and part of this effect can likely be attributed to CCR3-antagonism. The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis.Trial registrationEudraCT No: 2005-002805-21.

Identification of polymorphisms in the Toll-like receptor gene and the association with allergic rhinitis

The TLRs gene encodes the principal innate immunity receptor in humans. The TLR2 Arg753Gln and Arg677Trp polymorphisms have been associated with a reduced response of monocytes and cell lines to challenge with mycobacteria. The TLR4 Asp299Gly and Thr399Ile polymorphisms have been associated with a reduction in the inflammatory responses to lipopolysaccharide in humans. It has been suggested that TLR2 and TLR4 polymorphisms may be associated with allergic responses; thus, we hypothesized that TLR2 and TLR4 polymorphisms may modify the relative risk for development of allergic rhinitis. The Taqman assay and high-resolution melt (HRM) were used for genotyping. We analyzed two single nucleotide polymorphisms (SNPs; 597T>C and 1350T>C) in the TLR2 gene and 1 SNP (4216G>C) in the TLR4 gene. We compared the genotype of these SNPs in patients with allergic rhinitis and controls without allergic rhinitis. We also estimated the haplotype frequencies between the two groups. The genotype and allele frequencies of the 597T>C and 1350T>C SNPs in the TLR2 gene were not significantly different between the patients with allergic rhinitis and controls (P > 0.05). The genotype and allele frequencies of 4216G>C in the TLR4 gene were not significantly different between the patients with allergic rhinitis and controls (P > 0.05). Haplotype analysis of the following two different (597)-(1350) major haplotypes (frequency >0.05) were present in the TLR2 gene: T-C and C-C. The C-C haplotype was positively associated with allergic rhinitis (P = 0.048). Our study suggests that the TLR2 gene polymorphisms might be susceptible to the development of allergic rhinitis. Further functional studies of TLR2 genetics in light of the associations with allergic rhinitis inflammation would help clarify the role of TLR2 genetics in clinical evaluations.

Minimal persistent inflammation in allergic rhinitis: implications for current treatment strategies.

Patients with allergic rhinitis have traditionally been placed into 'seasonal' and 'perennial' categories, which do not account for the subclinical inflammatory state that exists in many patients. In subjects with seasonal and perennial allergic rhinitis, even subthreshold doses of allergen have been found to cause inflammatory cell infiltration in the nasal mucosa, including increases in expression of cellular adhesion molecules, nasal and conjunctival eosinophilia, and other markers of inflammation, which do not result in overt allergy symptoms. This state - which has been termed 'minimal persistent inflammation'- may contribute to hyperreactivity and increased susceptibility to development of clinical symptoms as well as common co-morbidities of allergic rhinitis, such as asthma. Treating overt allergy symptoms as well as this underlying inflammatory state requires agents that have well-established clinical efficacy, convenient administration, potent anti-inflammatory effects and proven long-term safety, so that long-term continuous administration is feasible. Of the three major classes of commonly used allergic rhinitis medications - intranasal corticosteroids, anti-histamines, and anti-leukotrienes - intranasal corticosteroids appear to represent the most reasonable therapeutic option in patients who would benefit from continuous inhibition of persistent inflammation.

Elevation Of Anti-inflammatory Mediator Sphingosine-1-phosphate Abrogate Inflammation In Allergic Rhinitis

RATIONALE: Sphingosine-1-phosphate (S1P) is an anti-inflammatory mediator and an important molecule for the egress of lymphocytes from lymphoid tissue into the circulation. S1P breakdown occurs rapidly due to sphingosine-lyase(SL) in tissue's, which can be inhibited by 2-acetyl-4-tetrahydroxybutyl(THI). The anti-inflammatory role of a S1P-analog-FTY720 and THI was studied in an ovalbumin(OVA) driven model of allergic rhinitis(AR). METHODS: OVA-alum sensitized animals were intranasal challenged with OVA during a 3 week period of 3 consecutive days per week. Animals were treated with (optima)l doses of 6ug FTY720 or 7.5ug THI or combined FTY720-THI or diluent. Nasal mucosal inflammation and cytokine production in OVA restimulated cervical lymph node cell suspensions (CLNs) were evaluated. RESULTS: FTY720 treatment showed significant less eosinophils and mast cells compared to diluent in the nasa[l mucosa of AR animals. IL-4, IL-5, IL-10, IL-13 and OVA specific IgE reduced significantly in FTY720 treated animals. Topical treatment with THI showed a strong reduction in mast cell numbers. Combined treatment of FTY720 and THI reduced eosinophil numbers and mast cell numbers in the nasal mucosa and reduced Th2 cytokines in CLNs in AR. Moreover, FTY720 showed to be potent enough to suppress the inflammation in a model of persistent AR. CONCLUSIONS: Elevation of the anti-inflammatory mediator S1P by adding a synthetic analog or by inhibiting the breakdown of natural occurred S1P has significant advantage to abrogate inflammation in AR. Our results may be translatable into new locally acting drugs as a powerful strategy for the treatment of AR in humans as an alternative for topical steroids treatment.

Inflammatory and oxidative stress biomarkers in allergic rhinitis: the effect of smoking

Accumulating evidence confirms the presence of pan-airway inflammation in allergic rhinitis patients. Smoking is known to affect the asthmatic airway inflammation. However, no study has evaluated the impact of smoking on airway inflammation of allergic rhinitis patients. The aim of the present study was to evaluate the impact of smoking on inflammatory and oxidative stress biomarkers in patients with seasonal allergic rhinitis, using non-invasive methods for sample collection. Forty patients with seasonal allergic rhinitis (20 smokers and 20 non-smokers) and 30 healthy subjects (15 smokers and 15 non-smokers) were recruited for the study during pollen season. All subjects were submitted to measurement of the fraction of exhaled NO (FeNO), exhaled breath condensate (EBC) collection, nasal lavage collection, pre- and post- bronchodilation spirometry and metacholine bronchial challenge testing. pH, leukotriene B(4) (LTB(4)) and 8-isoprostane were determined in EBC and nasal lavage samples. Patients with allergic rhinitis presented higher LTB(4) and 8-isoprostane levels in nasal lavage (P<0.0001 for both comparisons), with no significant differences between smokers and non-smokers. Patients with allergic rhinitis also presented higher LTB(4) levels and lower pH in EBC (P<0.001 and P=0.004, respectively), with prominent differences between smokers and non-smokers (P<0.0001 and P=0.003, for LTB(4) and pH, respectively). A significant correlation between nasal lavage and EBC LTB(4) values was observed (r(s)=0.313, P=0.048). Patients with allergic rhinitis present increased LTB(4) and 8-isoprostane in their nasal cavity, however, with no significant differences between smokers and non-smokers. In contrast, smokers with allergic rhinitis present higher LTB(4) levels and lower pH in EBC, suggesting that these patients may be more susceptible to the deleterious effects of smoking, compared with non-smokers.

Current status of intranasal glucocorticosteroids in the management of allergic rhinitis

SummaryGlucocorticosteroids are the most effective drugs for controlling inflammation of allergic rhinitis (AR). Because of their strong pharmacological action, which can be a so‐called ‘double‐edged sword’, glucocorticosteroids are usually taken intranasally so as to reduce their potential for eliciting adverse effects. Accumulating evidence suggests that intranasal glucocorticosteroids control not only nasal symptoms but also ocular symptoms. In contrast to sedating H1‐receptor antagonists, intranasal glucocorticosteroids can improve impaired performance such as daytime sleepiness associated with AR. In Japanese cedar pollinosis, treatment begun immediately after initiation of pollen release or onset of initial symptoms, known as prophylactic (initial) treatment, is recommended. The current version of the practical guideline for management of allergic rhinitis in Japan recommends the use of chemical mediator release inhibitors, second‐generation H1‐receptor antagonists, or leukotriene receptor antagonists for prophylactic treatment. However, recent evidence suggests that intranasal glucocorticosteroids might also be useful as first‐line drugs for prophylactic treatment. The molecular mechanism of anti‐inflammatory action of glucocorticosteroids supports this contention. Moreover, a meta‐analysis of studies of intranasal glucocorticosteroids given as monotherapy has revealed that these agents are superior to oral H1‐receptor antagonists and leukotriene antagonists for controlling major symptoms of AR. These findings suggest that glucocorticosteroids, especially intranasal glucocorticosteroids, might be positioned as first‐line drugs for the treatment of both perennial and seasonal AR.

Nasal eosinophils and reversibility to the decongestion test in patients with perennial allergic rhinitis

Nasal obstruction is sustained by eosinophilic inflammation in allergic rhinitis. The decongestion test consists of spraying an intranasal vasoconstrictor drug to evaluate the reversibility of nasal airflow limitation. The aim of this study was to assess the relationships of both the number of nasal eosinophils and the degree of nasal obstruction symptom with the reversibility of nasal airflow after the decongestion test in patients with perennial allergic rhinitis (PAR). Eighty-three patients with PAR were studied. Total symptom score, sensitization, rhinomanometry, and the decongestion test were performed in all the patients. Using multivariate analysis, the eosinophils number was significantly (and inversely) associated (p < 0.001) with the reversibility of nasal airflow, whereas the nasal obstruction symptom degree was not (p = 0.338). This study provides evidence of a significant association between nasal eosinophils and the reversibility to the decongestion test in patients with PAR.

Expression of uteroglobin in a murine model of allergic rhinitis

Conclusion. We observed for the first time the expression of Uteroglobin (UGB) in the nasal mucosa of mice. The results of our study suggest that UGB may play an important role in the regulation of inflammation in allergic rhinitis (AR) as well as in the lower airway allergic inflammations. Objectives. Uteroglobin is a protein secreted by epithelial lining of organs communicating with the external environment. Reports of its immunomodulatory effects in allergic disease have been made, but the true physiological role still remains to be elucidated. In this study we tried to observe the expression of UGB in the nasal mucosa of mice and determine its role in AR. Materials and Methods. Thirty BALB-c mice at 3 weeks of age (10 mice/group) were sensitized systemically by intraperitoneal ovalbumin injection and locally by ovalbumin inhalation. Control group were sensitized with PBS. Treatment group had intraperitoneal dexamethasone injection 1 hour before the initial sensitization while control and AR group were injected with PBS. Symptom scores, eosinophil counts, immunohistochemical staining as well as UGB mRNA expression in the nasal mucosa and lung tissue were analyzed. Results. The symptom scores and eosinophil counts between control and treatment group was significantly different from the AR group (P<0.01). On immunohistochemical staining, UGB was localized in the epithelium and submucosal gland of the nasal mucosa as well as in the epithelium of respiratory bronchioles. UGB mRNA expression of the nasal mucosa and lung tissue was decreased in the AR group compared to the control group (P=0.022). In the treatment group UGB expression was increased compared to the AR group (P=0.016). The results of IHC and mRNA expression in the lung tissue correlated with the results in the nasal mucosa.

Expression of Syk is associated with nasal polyp in patients with allergic rhinitis

Objective Numerous signalings are involved in allergic inflammation. The non-receptor protein tyrosine kinase, Syk, is widely expressed in immune-potentiated cells and plays critical roles in initiating signal transduction in response to the activation of cytokine, chemokine and other types of receptors. It has been hypothesized that Syk expression in allergic nasal mucosa and polyps with allergy is different from non-allergic mucosa, and that changes in Syk expression contribute to the activation of allergic reactions. Methods We examined whether the expression of Syk is found in allergic nasal mucosa and polyps. We investigated the expression of Syk in 46 nasal mucosa and polyps (14 samples from patients with allergic rhinitis and 32 samples with non-allergic chronic sinusitis) using an immunohistochemical technique. Results Allergic polyps had more Syk positive cells than non-allergic polyps. Syk positive cells were determined to mainly be eosinophils. There was no difference in Syk expression in the lamina propria and nasal gland between allergic mucosa and non-allergic mucosa. Conclusion Eosinophils in allergic polyps receive an intracellular signal, although the signal is not able to determine the function in the present state. Syk appears to be a promising target molecule for anti-allergic inflammation in allergic rhinitis.

Heme Oxygenase (HO)‐1 Is Upregulated in the Nasal Mucosa With Allergic Rhinitis

Heme oxygenase (HO) is considered to be an antioxidant enzyme that catabolizes heme to produce carbon monoxide (CO) and biliverdin. Three isoforms of HO have been discovered. Recently, HO-1 has been found to be upregulated after allergic inflammations of the lower airway. The objective of this study was to address the expression of HO isoenzymes 1 and 2 in the nasal mucosa of patients with allergic rhinitis as well as normal control subjects. Nasal mucosa from 30 patients with persistent allergic rhinitis as well as from 10 normal volunteers was used in this study. We used immunofluorescent technique, Western blotting, and real-time quantitative polymerase chain reaction to localize and quantify the expression of these isoenzymes in normal and allergic human nasal tissues. We found that HO-1 is expressed in the epithelial cells of seromucinous glands and macrophages with significant upregulation of its glandular expression in allergic rhinitis but with no difference in its macrophage expression between the study groups in contrast to HO-2 that is expressed in the vascular endothelial lining cells as well as macrophages with no marked difference between the study groups. We demonstrated that expression of HO-1, but not HO-2, was upregulated within the nasal tissues in allergic rhinitis inflammation, and understanding the induction of HO-1 expression may provide for better management of allergic rhinitis that involves oxidative stress.

Cysteinyl Leukotrienes in Allergic Inflammation*

Systemically bioavailable leukotriene receptor antagonists (LTRAs) can reduce the essential components of allergic inflammation in allergic rhinitis (AR) and asthma by blocking cysteinyl leukotriene (CysLT) activity, resulting in a wide range of clinical effects. CysLTs, mediators, and modulators in the pathophysiology of asthma and AR are a key target for therapy because they modulate production of hemopoietic progenitor cells, survival and recruitment of eosinophils to inflamed tissue, activity of cytokines and chemokines, quantity of exhaled NO, smooth-muscle contraction, and proliferation of fibroblasts. The mechanism of action of LTRAs leads to their effects on systemic allergic inflammatory processes.

Nasal Eosinophils Display the Best Correlation with Symptoms, Pulmonary Function and Inflammation in Allergic Rhinitis

Background: The pathogenesis of allergic rhinitis and its link with asthma are well known. Nevertheless, a complete cross-sectional evaluation of the usually available clinical, functional and immunological parameters has never been made. We assessed nasal symptoms and flow, cytology, cytokines, pulmonary function and methacholine positivity in a large number of patients with pure pollinosis. Methods: Young men presenting at a military hospital for routine follow-up were recruited for the study. They had to suffer from rhinitis alone (without asthma) for at least 2 years and had to have a positive skin prick test to pollens only. During the pollen season, they underwent symptom evaluation, measurement of nasal flow, nasal scraping and lavage (cell count and assay for IL-4, IL-5, IL-8 and IFNγ), pulmonary function tests and methacholine challenge. Results: Fifty subjects (23.7 ± 4.9 years old) were enrolled. All patients had high clinical scores (9.5 ± 1.6) and inflammatory cells (eosinophils: 10.5 ± 4 and neutrophils 21.3 ± 6) and low nasal flow (482 ± 111 ml/s). We found that the number of eosinophils in nasal scrapings highly correlated with all the above-mentioned parameters, including nasal flow, cytokines and spirometric values. A significant positive correlation was found between all inflammatory cells and all cytokines. IL-8, IL-4 and neutrophils displayed only a partial correlation with pulmonary parameters (FEV₁, FVC and FEF_25–75%), at variance wit IL-5 and eosinophils. Methacholine test positivity significantly correlated with the number of eosinophils in the nasal smear. Conclusion: Eosinophils in the nasal smear display the best correlation with all the clinical and immunological parameters in allergic rhinitis and also correlate well with methacholine response.