Markers Of Allergic Inflammation Research Articles

GPR120/FFAR4 stimulation attenuates airway remodeling and suppresses IL-4- and IL-13-induced airway epithelial injury via inhibition of STAT6 and Akt

BackgroundAirway remodeling is associated with severity and treatment insensitivity in asthma. This study aimed to investigate the effects of G protein-coupled receptor 120 (GPR120) stimulation on alleviating allergic inflammation and remodeling of airway epithelium. Research design and methodsOvalbumin (OVA)-challenged BALB/c mice and type-2-cytokine (IL-4 and IL-13)-exposed 16HBE human bronchial epithelial cells were treated with GSK137647A, a selective GPR120 agonist. Markers of allergic inflammation and airway remodeling were determined. ResultsGSK137647A attenuated inflammation and mucus secretion in airway epithelium of OVA-challenged mice. Stimulation of GPR120 in 16HBE suppressed expression of asthma-associated cytokines and cytokine-induced expression of pathogenic mucin-MUC5AC. These effects were abolished by co-treatment with AH7614, a GPR120 antagonist. Moreover, GPR120 stimulation in 16HBE cells reduced expression of fibrotic markers including fibronectin protein and ACTA2 mRNA and inhibited epithelial barrier leakage induced by type-2 inflammation via rescuing expression of zonula occludens-1 protein. Furthermore, GPR120 stimulation prevented the cytokine-induced airway epithelial remodeling via suppression of STAT6 and Akt phosphorylation. ConclusionsOur findings suggest that GPR120 activation alleviates allergic inflammation and remodeling of airway epithelium partly through inhibition of STAT6 and Akt. GPR120 may represent a novel therapeutic target for diseases associated with remodeling of airway epithelium, including asthma.

Risk factors and markers of inflammation of comorbid allergic diseases: rhinitis and bronchial asthma

Introduction. Today there has been a steady increase in the allergic pathology of the respiratory tract - bronchial asthma and allergic rhinitis in pediatric practice. Despite the use of modern diagnostic approaches, we cannot say with certainty which combined effect of which factors leads to the development of allergic inflammation of the respiratory tract. The study of risk factors for the formation of allergic rhinitis and asthma in children is necessary for timely early diagnosis with the subsequent development of an individual strategy for preventive measures.Objective: to study risk factors and markers of allergic inflammation in children with allergic rhinitis, rhinitis and bronchial asthma and only with bronchial asthma.Materials and methods. The study involved 107 children suffering from allergic rhinitis, allergic rhinitis and bronchial asthma, and only bronchial asthma. All patients underwent clinical, laboratory, functional, allergological examination, analysis of the cellular composition of bronchial and nasal secretions.Results. The analysis revealed factors influencing the development of bronchial asthma, allergic rhinitis and comorbid diseases, as well as markers of allergic inflammation. There were trends in detecting a higher level of eosinophils in blood, nasal and bronchial secretions in a group of children with a comorbid condition — bronchial asthma and allergic rhinitis.Conclusion. Evaluation of the level of markers of allergic inflammation of nasal and bronchial secretions can be used as additional criteria for early diagnosis, prediction of the severity of bronchial asthma and allergic rhinitis in children, serve as a monitoring method, development of personalized preventive measures for this group of children.

Показники цитокінового статусу дітей раннього віку з алергічним ураженням шлунково-кишкового тракту залежно від забезпеченості вітаміном D

The rapid growth in the prevalence of allergic diseases among children in the modern world dictates the need for detailed study of pathogenetic mechanisms, the search for new methods of diagnosis, treatment and prevention of this pathology. Recent studies of the important immunological effects of vitamin D in allergic pathology make it important to study its effect on the course of gastrointestinal food allergy (GIFA) in young children. Purpose - to determine the serum concentrations of IL-10 and IL-17 in young children with GIFA, depending on the supply of vitamin D. Materials and methods. We examined 34 children aged from 2 months to 3 years with isolated gastrointestinal symptoms or a combination of gastrointestinal and skin symptoms associated with food. The comparison group consisted of 22 children of the same age with an unencumbered individual and family history of allergies. All examined children had quantified serum cytokine (IL-10, IL-17A) levels by enzyme-linked immunosorbent assays and serum hydroxycalciferol (25(OH)D) levels. Vitamin D deficiency in subjects was considered at a concentration of 25(OH)D in serum <20 ng/ml (or <50 nmol/l), a concentration of 21 ng/ml to 29 ng/ml (or from 50.1 nmol/l up to 74.9 nmol/l) was assessed as vitamin D deficiency. A sufficient concentration of vitamin D was considered to be 25(OH)D serum level >30 ng/ml. Data of clinical and laboratory researches were processed by methods of mathematical statistics accepted in biology and medicine. Results. There was a significantly increase in the average concentrations of IL-17A (180.4±23.0 pg/ml) and IL-10 (113.8±15.0 pg/ml) in children with gastrointestinal food allergy and in the comparison group - 45.7±18.1 pg/ml and 32.1±11.4 pg/ml, respectively, (p<0.05), which reflects the intensity of the allergic inflammatory process in the gastrointestinal tract. In children with allergic gastrointestinal inflammation who were deficient in vitamin D, the mean concentrations of proinflammatory cytokine IL-17A and regulatory cytokine IL-10 were significantly higher than in children with GIFA and optimal supply of vitamin D 244.9±19.7 ng/ml and 49.45±2.14 ng/ml respectively against 135.2±33.3 ng/ml and 26.41±1.81 ng/ml respectively, (p<0,05), which indicates a more intense activity of the inflammatory process in the intestine of children with insufficient supply of vitamin D. Conclusions. Allergic gastrointestinal inflammation in young children is characterized by increased concentrations of serum proinflammatory and regulatory cytokines - IL-10 and IL-17A, that is a protective reaction of the immune system and can be used as a marker of allergic inflammation in GIFA. The study of the regulatory effect of vitamin D on the expression of cytokines (IL-10 and IL-17A) in allergic gastrointestinal inflammation in young children will optimize the pathogenetic treatment of gastrointestinal food allergies. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors. Key words: cytokine status, young children, allergic pathology of the gastrointestinal tract, vitamin D.

THE DIAGNOSTIC VALUE OF ALLERGIC INFLAMMATION MARKERS IN INFANTS WITH BRONCHIOLITIS

Introduction. It is quite important to study the markers of allergic inflammation depending on the status of vitamin D in order to understand the pathogenetic links of bronchiolitis in infants.Aim of study. Analysis of the relationship between serum vitamin D levels and indicators of allergic inflammation (eosinophil cationic protein (ECP) and IgE) in infants with bronchiolitis.Materials and methods. A clinical examination of 55 infants was conducted. The main group consisted of 25 children with bronchiolitis who had a history of allergies. The comparison group consisted of 20 children with bronchiolitis without a burdensome allergy history. The control group included 10 relatively healthy children. The mean age of children in the main group was 7.2 ± 1.4 months, 6.4 ± 1.2 months in the comparison group, and 9.2 ± 1.6 months in the control group.Results of the study. It was found that the duration of hospital stay in children of the main group was 8.2 ± 1.32 days, while in children of the comparison group the duration of stay in hospital was significantly shorter (p <0.05). We found a significant difference in the indicators of allergic inflammation that depended on the status of vitamin D in the examined children. Thus, in children with vitamin D deficiency and insufficiency, a marked increase in ECP (56.3 ± 12.8 ng / ml) and total IgE levels to 127.5 ± 3.12 IU / ml was found compared to the same indicators as in children of the main group with the optimal level of 25 (OH) D, and in children of the comparison group, p˂0,001. It should be noted that the rate of allergic inflammation marker ECP in children of the comparison group with deficiency and insufficiency of vitamin D in serum also had a significant difference when compared with infants of the control group, p˂0.05. Conclusions. In children with bronchiolitis, obtained history of allergies and insufficient levels of vitamin D and its insufficiency, the severity of the disease is manifested by a longer duration of clinical symptoms and hospital stay. Eosinophilic cationic protein can be considered as a marker of allergic inflammation in infants with bronchiolitis.

Are Markers of Allergic Inflammation in Grass Pollen Allergy Influenced by H1 Antihistamines?

Soluble intercellular adhesion molecule-1 (ICAM-1) and soluble vascular adhesion molecule-1 (VCAM-1) play important roles in allergic rhinitis (AR). Treatment with H1 antihistamines improves AR symptoms and in vitro reduces the levels of adhesion molecules. The aim of the study was to evaluate serum levels of ICAM-1 and VCAM-1 in patients with AR to grass pollen and their response to different H1 antihistamines. Material and methods: A total of 50 patients with grass pollen AR were clinically and biologically evaluated. ICAM-1 and VCAM-1 serum levels were evaluated during pollen season before and after treatment with levocetirizine and desloratadine through the ELISA method. Results: ICAM-1, VCAM-1, eosinophils, and total IgE were elevated in patients with AR, compared with healthy subjects. Both antihistamines improved specific symptoms of AR and increased patients’ quality of life during pollen season after one month of treatment. H1 antihistamines reduced VCAM-1, ICAM-1, and total IgE after one-month treatment but not significantly. Patients with increased baseline values tend to remain with increased values after one-month AH1 treatment. Conclusions: ICAM-1 and sVCAM-1 levels are higher in patients with grass pollen-induced AR than healthy controls during pollen exposure. Their serum levels tend to remain at high values during pollen season despite antihistaminic therapy.

Interleukin-13 as a Marker of Allergic Inflammation in Patients with Fungal Asthma

Fungal asthma (FA) is characterized by frequent exacerbations, rapidly growing irreversible changes in distal bronchi with 10% of FA failing inhaled glucocorticosteroids requiring systemic steroids. Immune markers of FA are needed.

Assessment of asthma risk in patients with allergic rhinitis

The evolution from allergic rhinitis to asthma was reported in numerous studies referred as “atopic march”. Often those two diseases coexist and represent a single disease of an allergic patient, so named “the united airways disease”. The question “Which patients with allergic rhinitis will develop asthma?” is important for all the physicians which are taking care of allergies. Genetic studies showed a number of genes which are involved in allergic diseases occurrence, but it is also important the influence of the environment. The aim of this study was to evaluate if some inflammatory markers may predict the occurrence of asthma in patients with allergic rhinitis. We studied a group of 75 patients with persistent allergic rhinitis. The initial clinical evaluation was done at the beginning of the study, referring to disease severity and sensitization. The FENO measurement was performed to all patients with allergic rhinitis. The serum levels of ICAM-1, E-selectine and VCAM-1, IL-6, IL-8 and TNF-α were determined using ELISA method. The same group was clinically evaluated after one year, in order to determine the presence of asthma symptoms and to establish diagnose of bronchial asthma. The markers of allergic inflammation, total IgE and eosinophils were higher in patients who developed asthma after 1 year, compared to patients with allergic rhinitis without asthma, but the differences were not statistically significant (p>0.05). We noticed similar results for adhesion molecules (ICAM, VCAM and E-selectin) and IL-6, but not for TNF-α and IL-8. Only FeNO was significantly higher in patients with allergic rhinitis and asthma compared to those without asthma (p<0.001). FENO and some proinflammatory cytokines may predict the occurrence of asthma in patients with allergic rhinitis. This study also underlines the importance for asthma evaluation in patients with allergic rhinitis.

Effect of inhaled corticosteroids on serum periostin levels in adult patients with mild-moderate asthma.

Background: Periostin is an extracellular matrix protein, and its expression is upregulated in airway epithelial cells in patients with bronchial asthma. Periostin may be a key molecule linked to type 2 T-helper cell inflammation. Inhaled corticosteroids (ICS) may suppress periostin-induced asthmatic inflammation. This study estimated the serum periostin levels in patients with asthma and evaluated the effect of ICS on the levels of periostin, peak expiratory flow rate (PEFR), and quality of life (QOL). Methods: The study design was prospective, open label, and observational. Forty adults with mild-to-moderate bronchial asthma started on ICS and matched healthy controls were enrolled. The patients were evaluated for their serum periostin, PEFR, and QOL by using asthma QOL questionnaire scores at baseline and after 4 weeks. Results: The mean ± standard deviation (SD) serum periostin concentration in patients with asthma was 90.36 ± 19.81 ng/mL, which was significantly higher (p < 0.01) compared with healthy controls (31.88 ± 8.71 ng/mL). ICS treatment for 4 weeks reduced the mean ± SD serum periostin levels to 58.78 ± 14.53 ng/mL. The mean ± SD PEFR increased significantly, from 225.25 ± 60.79 L/min to 292.5 ± 59.18 L/min (p < 0.01), after 4 weeks. Similarly, the mean ± SD when using asthma QOL questionnaire scores significantly increased, from 40.7 ± 7.84 at baseline to 59.33 ± 11.0 on day 28 after ICS therapy (p < 0.01). Conclusion: The serum periostin level, a marker of allergic inflammation and remodeling, increased in bronchial asthma and was reduced with ICS therapy. ICS improved QOL scores and PEFR in patients with asthma.

Soluble CD93 in Serum as a Marker of Allergic Inflammation.

PurposeCD93 is receiving renewed attention as a biomarker of inflammation. We aimed to evaluate the potential for serum sCD93 to serve as a novel biomarker for allergic inflammation.Materials and MethodsWe enrolled 348 subjects with an allergic disease [allergic rhinitis (AR), chronic spontaneous urticaria (CSU), or bronchial asthma (BA)], including 14 steroid-naïve BA patients who were serially followed-up.ResultsThe serum sCD93 levels (ng/mL) in patients with exacerbated AR (mean±standard deviation, 153.1±58.4) were significantly higher than in patients without AR (132.2±49.0) or with stable AR (122.3±42.1). Serum sCD93 levels in exacerbated CSU (169.5±42.8) were also significantly higher than those in non-CSU (132.4±51.6) and stable CSU (122.8±36.2). This trend was also seen in BA. Serum levels in patients with ICS-naïve BA (161.4±53.1) were significantly higher than those in healthy controls without BA (112.2±30.8), low- and medium-dose ICS users. Serum sCD93 levels in high-dose ICS users (72.2±20.6) were significantly lower than those in low- and medium-dose users. The serum sCD93 levels in steroid-naïve patients with BA (195.1±72.7) decreased after ICS use for 4 weeks (134.4±42.8) and 8 weeks (100.7±13.4), serially.ConclusionElevated serum sCD93 levels reflected exacerbated status of allergic diseases, including CSU, AR, and asthma. ICS use significantly diminished serum sCD93 levels in steroid-naïve patients with BA. This result may suggest sCD93 in serum as a therapeutic marker for allergic inflammation.

Effect of controlled human exposure to diesel exhaust and allergen on airway surfactant protein D, myeloperoxidase and club (Clara) cell secretory protein 16.

Air pollution is a major cause of global morbidity and mortality. Air pollution and aeroallergens aggravate respiratory illness, but the variable effects of air pollutants and allergens in the lung are poorly understood. To determine the effects of diesel exhaust (DE) and bronchial allergen challenge as single and dual exposures on aspects of innate immunity in the airway as reflected by surfactant protein D (SPD), myeloperoxidase (MPO) and club (Clara) cell secretory protein 16 (CC16) in 18 atopic individuals. In this double-blind, randomized crossover study, atopic individuals were exposed to DE or filtered air, followed by endobronchial allergen or saline 1 hour after inhalational exposure. Bronchoalveolar lavage, bronchial washings, nasal lavage and blood samples were obtained 48 hours after exposures and assayed for CC16, MPO and SPD by ELISA. In bronchial samples, the concentration of SPD increased from 53.3 to 91.8 ng/mL after endobronchial allergen, with no additional contribution from DE. MPO also increased significantly in response to allergen (6.8 to 14.7 ng/mL), and there was a small additional contribution from exposure to DE. The concentration of CC16 decreased from 340.7 to 151.0 ng/mL in response to DE, with minor contribution from allergen. These changes were not reflected in nasal lavage fluid or plasma samples. These findings suggest that allergen and DE variably influence different aspects of the innate immune response of the lung. SPD and MPO, known markers of allergic inflammation in the lung, are strongly increased by allergen while DE has a minor effect therein. DE induces a loss of CC16, a protective protein, while allergen has a minor effect therein. Results support site- and exposure-specific responses in the human lung upon multiple exposures.

Inflammation Markers and FEF25-75: A Relevant Link in Children With Asthma.

Jang and colleagues investigated the relationship between exhaled nitric oxide (FeNO) and atopy profiles in children with asthma.1 They focused their attention mainly on the FeNO, showing that this parameter varied according to the profile of atopy. The authors also investigated lung function, including bronchial hyperreactivity. However, forced vital capacity, forced expiratory volume in 1 second (FEV1), and their ratio were considered as parameters for lung function test. On the other hand, great attention has been recently paid to the relevance in asthma pathogenesis of FEF25-75 values,2 a parameter considered to better reflect small airways than the gold standard parameters of airway obstruction, such as forced vital capacity and FEV1.2 This may be even more relevant in childhood.3 Indeed, in allergic children with asthma, impaired FEF25-75 values appear to be related to severe bronchial hyperreactivity,4 reversible airway obstruction;5 perception of breathlessness and of positive response to reversibility test, assessed by visual analogue scale.6,7 Since impaired FEF25-75 values were reported to be significantly associated also with the presence of high fractional FeNO levels in children with allergic rhinitis and/or asthma,8 it is possible that this marker of small airway obstruction could be related also to the degree of allergic sensitization (and of systemic allergic inflammation). Previously, it has been reported that children with asthma due to mite allergy showed a tightly link between allergen-specific serum IgE and markers of allergic inflammation, such as eosinophil and FeNO, but no correlations were detected with bronchial obstruction, expressed as FEV1 values.9 On the basis of these considerations, we evaluated a cohort of children with allergic asthma, sensitized to house dust mites, aiming at investigating possible relationship between lung function, mainly concerning FEF25-75, and inflammation parameters, such as blood eosinophilia, allergen-specific serum IgE, and FeNO. Fifty-six children, 5 to 12 years of age, were studied. Blood eosinophil number inversely and moderately related with FEF25-75 values (r=-0.52; P<0.0001), as reported in Figure A. Also the relative blood eosinophil numbers, expressed as percentage on total blood leukocytes count, significantly and negatively correlated with FEF25-75 values (r=-0.4; P=0.001) (Figure B). Serum levels of house dust mites specific IgE showed negative significant correlations with FEF25-75 values (r=-0.31; P=0.01), as reported in Figure C. Finally, a significant negative relationship was demonstrated between FeNO and FEF25-75 values (r=-0.33; P=0.01) (Figure D). In contrast, a significant negative correlation with FEV1 values was detected only for blood eosinophil numbers (r=-0.35; P=0.006). These findings further confirm the possibility to detect links between markers of allergic inflammation and airflow limitation and further support the importance of FEF25-75 assessment in the evaluation of childhood allergic asthma. Figure Relationship between FEF25-75 values and different inflammatory/allergy markers: blood eosinophils (as absolute number, A; as relative number, B), serum IgE to house dust mites (C), and FeNO (D).

Effect Of Melatonin In A Rat Model Of Allergic Lung Inflammation

Aims: Asthma is an inflammatory lung disease characterized by bronchoconstriction and hyper responsiveness. Immuno stimulatory effects of melatonin have been reported. In this study, we investigated the impact of melatonin administration on allergic airway inflammation in a rat model. Methods: Forty five adult Wistar albino rats were equally divided into three groups: group I served as control; group II: rats sensitized to ovalbumin and challenged intranasally with ovalbumin to induce an allergic inflammatory response and group III, rats were sensitized and treated with intraperitoneally melatonin. The serum levels of IgE, IgG1 and ova-specific IgG were measured by ELISA. In the bronchoalveolar lavage fluid (BALF), the levels of IL-4, IL-5, IL-13, 1L-10 were measured. IL-10 expression was measured by real time polymerase chain reaction. Histopathological examination of the lung tissues using H&E stain were done. Results: Melatonin administration inhibited allergen-induced lung eosinophilic infiltration and improved the pathological lesions of the lungs. It significantly decreased total serum IgE, IgG1 and OVAspecific IgG1 along with BALF levels of IL-4, IL-5, IL-13. Melatonin increased BALF levels of IL-10 and its mRNA expression. Conclusion: Melatonin administration exhibited a significant reduction in all the markers of allergic inflammation. The data suggests that inhibition of T-cell response and up regulation of IL-10 may be responsible for immunomodulatory effect of melatonin in the rat model of allergic airway inflammation.

P56 ‐ Control of allergic inflammation and erythrocytes magnesium level in children with bronchial asthma

Results Patients comparison groups had comparable levels of clinical control of asthma by AST-test. In determining the level of nitric oxide in exhaled air were obtained pre-credibility of the differences between the groups. A more pronounced level of allergic inflammation in patients 2 groups confirmed higher concentrations of its laboratory markers. In determining the level of magnesium in red blood cells have lower it with the content of the group 2 patients. Conclusions The study revealed the discrepancy between clinical asthma control level and laboratory markers of allergic inflammation. In patients with longer experience of the disease on a background of basic therapy revealed higher levels of allergic inflammation and lower levels of magnesium in erythrocytes. Pharmacological correction of magnesium levels may be useful to improve the efficiency of basic therapy of asthma and achieve control of allergic inflammation.

Nasal nitric oxide is dependent on sinus obstruction in allergic rhinitis

The aim of this study was to evaluate the associations between nasal nitric oxide and nasal symptoms, sinus opacification, and markers of allergic inflammation in allergic and in nonallergic rhinitis while taking into account the effect of sinus obstruction. We studied 175 young adult subjects divided into three groups: 1) allergic rhinitis, 2) nonallergic rhinitis, and 3) controls. We measured nasal nitric oxide using the breath-holding method and exhaled nitric oxide and scored semiquantitatively nasal computed tomography scans for opacification and obstruction. We also assessed the visual analogue scores of nasal symptoms, eosinophil count, and interleukin-13 mRNA levels in nasal biopsies. The level of nasal nitric oxide correlated with exhaled nitric oxide (r = 0.377, P < .001). In allergic rhinitis, nasal nitric oxide was elevated when compared to the controls, and an inverse correlation existed between the nasal nitric oxide level and sinus ostial obstruction (r = -0.272, P = .013). In nonallergic rhinitis, the level of nasal nitric oxide was similar to that of the controls. In allergic rhinitis, nasal nitric oxide correlated positively with the opacification score (r = 0.250, P = .033) and the nasal eosinophil count (r = 0.293, P = .030) of patients without a marked sinus ostial obstruction. Sinus ostial obstruction lowers the level of nasal nitric oxide and reduces its value as an indicator of allergic mucosal inflammation. A high nasal nitric oxide level may be a useful marker of eosinophilic inflammation in the nasal cavity and indicate the absence of marked sinus ostial obstruction. 3b.

Analyzing Serum Eosinophil Cationic Protein in the Clinical Assessment of Chronic Rhinosinusitis

Eosinophil cationic protein (ECP) is a major granule-derived protein with cytotoxic activity found in eosinophils and has been known as a useful marker of allergic inflammation. In this study, we assessed the clinical significance of ECP in chronic inflammation of the nasal mucosa by evaluating the relationship between eosinophil activity and serum ECP concentration in a cohort of subjects with or without chronic rhinosinusitis (CRS) and allergic rhinitis (AR). We retrospectively reviewed the medical records of 492 subjects and analyzed eosinophil percentage in nasal smears, serum eosinophil counts, serum ECP concentrations, symptom scores, CT scores, the size of nasal polyp, and recurrence of CRS at follow-up. Elevated serum ECP concentration was closely related with higher eosinophil expression in all subject's nasal smears and sera. CRS subjects without AR had a higher percentage of immune cells that were eosinophils compared with control subjects and it was similar to subjects' with AR only or with both CRS and AR. CRS subjects without AR also had significantly higher serum ECP concentrations and eosinophil counts compared with control subjects. Additionally, serum ECP concentration was significantly correlated with CT scores, symptom scores, polyp size, and recurrence rate in CRS subjects without AR. Serum ECP concentration can be used as a marker of local and systemic eosinophil expression. We conjecture that although serum ECP elevation may not be specific in AR, analysis of serum ECP concentration could be particularly useful in estimating the progression and prognosis of CRS.

Modulation of NF-κB and Hypoxia-Inducible Factor−1 byS-Nitrosoglutathione Does Not Alter Allergic Airway Inflammation in Mice

Induction of nitric oxide synthase (NOS)-2 and production of nitric oxide (NO) are common features of allergic airway disease. Conditions of severe asthma are associated with deficiency of airway S-nitrosothiols, a biological product of NO that can suppress inflammation by S-nitrosylation of the proinflammatory transcription factor, NF-κB. Therefore, restoration of airway S-nitrosothiols might have therapeutic benefit, and this was tested in a mouse model of ovalbumin (OVA)-induced allergic inflammation. Naive or OVA-sensitized animals were administered S-nitrosoglutathione (GSNO; 50 μl, 10 mM) intratracheally before OVA challenge and analyzed 48 hours later. GSNO administration enhanced lung tissue S-nitrosothiol levels and reduced NF-κB activity in OVA-challenged animals compared with control animals, but did not lead to significant changes in total bronchoalveolar lavage cell counts, differentials, or mucus metaplasia markers. Administration of GSNO also altered the activation of hypoxia-inducible factor (HIF)-1, leading to HIF-1 activation in naive mice, but suppressed HIF-1 activation in OVA-challenged mice. We assessed the contribution of endogenous NOS2 in regulating NF-κB and/or HIF-1 activation and allergic airway inflammation using NOS2(-/-) mice. Although OVA-induced NF-κB activation was slightly increased in NOS2(-/-) mice, associated with small increases in bronchoalveolar lavage neutrophils, other markers of allergic inflammation and HIF-1 activation were similar in NOS2(-/-) and wild-type mice. Collectively, our studies indicate that instillation of GSNO can suppress NF-κB activation during allergic airway inflammation, but does not significantly affect overall markers of inflammation or mucus metaplasia, thus potentially limiting its therapeutic potential due to effects on additional signaling pathways, such as HIF-1.

Altered oxidative state in schoolchildren with asthma and allergic rhinitis

Oxidative stress may be defined as a disruption of the balance between the level of oxidants and reductants (antioxidants), and oxidative state in children may influence the risk of asthma and allergic disease. We investigated serum antioxidant levels: selenium, vitamin E, bilirubin, albumin, uric acid and transferrin as well as the oxidant ferritin and their association with asthma and allergic rhinitis. Children of 7-12 yr with asthma (n = 50) and no asthma (controls) (n = 52) underwent skin prick test, lung function, fractional exhaled nitric oxide (FeNO) measurements and blood sampling. Allergic rhinitis was found in 23 children, 19 with asthma and four controls. Healthy children were controls without rhinitis. Asthma was associated with reduced albumin (g/l), adjusted odds ratio (aOR) (95% CI) 0.81 (0.66, 0.99) (p = 0.048) compared with healthy children in a regression analysis adjusted for age and gender. Asthma with high FeNO ≥20 ppb was associated with reduced albumin, aOR 0.60 (0.40, 0.89) (p = 0.012) compared to controls with FeNO <20. Asthma with allergic rhinitis had reduced albumin, aOR = 0.70 (0.50, 0.99) (p = 0.04), and higher ferritin levels (mg/l) [aOR = 1.04 (1.00, 1.09) p = 0.03] compared to healthy children. Poorly controlled asthma was associated with lower vitamin E levels, aOR 0.79 (0.65, 0.95) (p = 0.02), lower transferrin levels, aOR 0.72 (0.57, 0.92) (p < 0.01), and higher albumin levels, aOR 1.53 (1.03, 2.28) (p = 0.04), compared to well controlled asthma. In conclusion, schoolchildren with asthma and rhinitis had reduced levels of the major serum antioxidant albumin, and poorly controlled asthma was associated with decreased vitamin E and transferrin levels. Reduced albumin was associated with increased FeNO, a marker of allergic inflammation in asthma, although the discriminatory value of this finding should be further assessed in population studies.

Local production of total IgE and specific antibodies to the house dust mite in adenoid tissue

Adenoids are known as immunosecretory organs and those in atopic children present cellular and cytokine profiles different from those of non-atopic children. We hypothesized that locally produced total IgE and allergen-specific antibodies could be involved in the inflammatory responses in adenoid tissue. Local productions of total IgE and Dermatophagoides pteronyssinus (DP)-specific IgE, IgA, IgG1, and IgG4 antibodies were evaluated, as well as their relationships with the markers of allergic inflammation within adenoid tissue. Eighteen atopic subjects, who were sensitized to more than one common aeroallergen, and 22 non-atopic subjects undergoing adenotonsillectomy, were recruited. Immunoassays using adenoid tissue homogenate were performed to quantify the levels of total IgE, eosinophil cationic protein (ECP), and mast cell tryptase. DP-specific IgE, IgA, IgG1, and IgG4 antibodies, soluble IL-2 receptors (sIL-2R), soluble CD23 (sCD23), and IL-6 were measured by ELISA. All parameters measured in adenoid tissue homogenate were presented as a ratio to the albumin level found in the adenoid. Median level of total IgE in adenoid tissue homogenate was significantly higher in atopic individuals than in non-atopic individuals. Median values of DP-specific IgE and IgA antibodies were significantly higher in atopics than in non-atopics (p = 0.001, p = 0.006, respectively), while no differences were seen in DP-specific IgG1 and IgG4 antibodies. ECP and sCD23 levels in adenoid homogenate were significantly higher in atopics than in non-atopics (p = 0.026, p = 0.048, respectively), while no significant differences were noted in tryptase, sIL-2R, and IL-6 levels. The levels of DP-specific IgE, IgA, IgG1, and IgG4 antibodies in adenoid homogenate correlated significantly with ECP levels, but not with those of sIL-2R, sCD23, and IL-6. The presence of total IgE and DP-specific antibodies in adenoid tissue was confirmed to be more prominent in atopics. In conclusion, locally-produced total IgE and DP-specific antibodies may contribute to eosinophilic inflammation in adenoid tissue in atopic children.

IgE response to staphylococcal enterotoxins in adenoid tissues from atopic children

To evaluate local production of staphylococcal superantigen (SAg)-specific IgE in adenoid tissue and to compare its prevalence with that in the tonsil and serum, as well as its relationship with markers of allergic inflammation within adenoid tissue. Prospective randomized study. We recruited 18 atopic children who had rhinitis symptoms and were sensitized to more than one common aeroallergen, and 22 nonatopic children undergoing adenotonsillectomy. Immunoassays were performed using adenoid tissue homogenate to quantify the levels of three staphylococcal SAg-specific IgE (SEA, SEB, and TSST-1), total IgE, eosinophil cationic protein (ECP), mast cell tryptase, and soluble CD23. Three kinds of SAg-specific IgE were detected in the adenoid and tonsil tissues of atopic patients, but not in those of nonatopic patients. In atopic children, the prevalence of SEA-, SEB-, and TSST-1-specific IgE in adenoid tissues (61.1%, 27.8%, 33.3%, respectively) were higher than those in tonsil tissues (38.9%, 5.6%, 11.1%, respectively) and in sera (11.1%, 27.8%, 16.7%, respectively). Subjects with high SEA levels showed significantly higher serum and adenoid total IgE, with higher eosinophilia. Significant correlations were noted between SAg-specific IgE levels and tryptase levels in adenoid tissue. Local specific IgE response to staphylococcal SAgs, especially SEA may contribute to ongoing allergic inflammation in adenoid tissue from atopic children.

Black seed oil ameliorates allergic airway inflammation by inhibiting T-cell proliferation in rats

The black seeds, from the Ranunculaceae family, have been traditionally used by various cultures as a natural remedy for several ailments. In this study, we examined the effect of black seed oil as an immunomodulator in a rat model of allergic airway inflammation. Rats sensitized to ovalbumin and challenged intranasally with ovalbumin to induce an allergic inflammatory response were compared to ovalbumin-sensitized, intranasally ovalbumin-exposed rats pretreated with intraperitoneally administered black seed oil and to control rats. The levels of IgE, IgG1 and ova-specific T-cell proliferation in spleen were measured by ELISA. The pro-inflammatory cytokine IL-4, IL-5, IL-6 and TGF-β1 mRNA expression levels were measured by reverse transcription polymerase chain reaction. The intraperitoneal administration of black seed oil inhibited the Th2 type immune response in rats by preventing inflammatory cell infiltration and pathological lesions in the lungs. It significantly decreased the nitric oxide production in BALF, total serum IgE, IgG1 and OVA-specific IgG1 along with IL-4, IL-5, IL-6 and TGF-β1 mRNA expression. Black seed oil treatment resulted in decreased T-cell response evident by lesser delayed type hypersensitivity and lower T-cell proliferation in spleen. In conclusion, black seed oil exhibited a significant reduction in all the markers of allergic inflammation mainly by inhibiting the delayed type hypersensitivity and T-cell proliferation. The data suggests that inhibition of T-cell response may be responsible for immunomodulatory effect of black seed oil in the rat model of allergic airway inflammation.