RESUMO
Cycloastragenol (CAG), a secondary metabolite from the roots of Astragalus zahlbruckneri, has been reported to exert antiinflammatory effects in heart, skin and liver diseases. However, its role in asthma remains unclear. The present study aimed to investigate the effect of CAG on airway inflammation in an ovalbumin (OVA)induced mouse asthma model. The current study evaluated the lung function and levels of inflammation and autophagy via measurement of airway hyperresponsiveness (AHR), lung histology examination, inflammatory cytokine measurement and western blotting, amongst other techniques. The results demonstrated that CAG attenuated OVAinduced AHR in vivo. In addition, the total number of leukocytes and eosinophils, as well as the secretion of inflammatory cytokines, including interleukin (IL)5, IL13 and immunoglobulin E were diminished in bronchoalveolar lavage fluid of the OVAinduced murine asthma model. Histological analysis revealed that CAG suppressed inflammatory cell infiltration and goblet cell secretion. Notably, based on molecular docking simulation, CAG was demonstrated to bind to the active site of autophagyrelated gene 4microtubuleassociated proteins light chain 3 complex, which explains the reduced autophagic flux in asthma caused by CAG. The expression levels of proteins associated with autophagy pathways were inhibited following treatment with CAG. Taken together, the results of the present study suggest that CAG exerts an antiinflammatory effect in asthma, and its role may be associated with the inhibition of autophagy in lung cells.
Assuntos
Antiasmáticos/farmacologia , Asma/etiologia , Autofagia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Sapogeninas/farmacologia , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Proteínas Relacionadas à Autofagia/antagonistas & inibidores , Proteínas Relacionadas à Autofagia/química , Proteínas Relacionadas à Autofagia/metabolismo , Biomarcadores , Biópsia , Hiper-Reatividade Brônquica/tratamento farmacológico , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/metabolismo , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Camundongos , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/química , Proteínas Associadas aos Microtúbulos/metabolismo , Sapogeninas/química , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Atopic sensitization belongs to the most common risk factors for bronchial asthma. However, in clinical practice, it is not clear whether sensitization against pollen and perennial allergens is differently associated with the severity of bronchial hyperresponsiveness (BHR). AIM: To find out whether patients sensitized to perennial allergens differ in severity of bronchial hyperresponsiveness from patients sensitized to pollen allergens. METHODS: The study includes 109 patients. Based on the results of skin prick tests, patients were divided into three groups: sensitivity to pollen allergens - group A; sensitivity to perennial allergens - group B; sensitivity to both pollen and perennial allergens - group C. Based on the histamine bronchoprovocation test, we compared the values of histamine provocative concentration causing a 20% drop in FEV1 (PC20) among particular groups of patients. Mild bronchial hyperresponsiveness was determined if the value of PC20 was >4 mg/ml, while if the value of PC20 was <4 mg/ml, the bronchial hyperresponsiveness was considered as moderate/severe. RESULTS: A statistically significant difference was found in the degrees of bronchial hyperresponsiveness between the three groups of patients, namely, group A with the patients sensitized only to the pollen allergens, group B comprising patients sensitized to the perennial allergens only, and group C, involving patients sensitized to the combination of both pollen and perennial allergens. The PC20 values were higher among the patients from the group A (7.46 mg/ml) compared to group B (4.25 mg/ml) and C (4.52 mg/ml). The odds ratio for moderate/severe BHR was 5.21 and 5.04 in group B and group C, respectively. CONCLUSION: Severity of bronchial hyperresponsiveness shows differences according to sensitization to particular allergens. Perennial allergens are more often associated with serious forms of bronchial hyperresponsiveness which also have an impact on the severity and prognosis of bronchial asthma.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Alérgenos/efeitos adversos , Hiper-Reatividade Brônquica/etiologia , Adolescente , Adulto , Hiper-Reatividade Brônquica/diagnóstico , Testes de Provocação Brônquica , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pólen/efeitos adversos , Eslováquia , Adulto JovemRESUMO
Cigarette smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD). However, little is known about the mechanisms of cigarette smoke-induced bronchial smooth muscle (BSM) hyperresponsiveness. In the present study, we investigated the effects of aqueous cigarette smoke extract (ACSE) on the BSM contraction in rats. The bronchial strips of rats were incubated with ACSE or control-extract for 24 h. The acetylcholine (ACh), high K(+) depolarization and sodium fluoride (NaF)-induced BSM contraction of the ACSE-treated group was significantly augmented as compared to that of the control one. The expression levels of both myosin light-chain kinase (MLCK) and RhoA were significantly increased in the ACSE-treated BSM. These findings suggest that the water-soluble components of cigarette smoke may cause BSM hyperresponsiveness via an increase in MLCK and RhoA.
Assuntos
Brônquios/efeitos dos fármacos , Hiper-Reatividade Brônquica/etiologia , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Nicotiana/química , Extratos Vegetais/efeitos adversos , Fumar/efeitos adversos , Animais , Técnicas In Vitro , Masculino , Músculo Liso Vascular/metabolismo , Quinase de Cadeia Leve de Miosina/metabolismo , Ratos Wistar , Água , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
Emissions of laser printers and photocopiers (LP&P) may be associated with health problems. The aim of this review is to describe the clinical picture that is triggered by exposure to LP&P and the molecular mechanisms underpinning the symptoms. Exposure to LP&P to vulnerable subjects may cause a symptom complex consisting of 1) irritation and hyperresponsiveness of the upper and lower respiratory tract; and 2) chronic fatigue (syndrome, CFS). Symptoms occur within hours after L&P exposure and may last for some days or become chronic with exacerbations following LP&P exposure. Substances that can be found in toners or are generated during the printing process are Silica nanoparticles, Titanium Dioxide nanoparticles, Carbon Black, metals, ozone, volatile organic compounds (VOC), etc. The latter may generate oxidative and nitrosative stress (O&NS), damage-associated molecular patterns molecules, pulmonary and systemic inflammation, and modulate Toll Like Receptor 4 (TRL4)related mechanisms. It is concluded that LP&P emissions may cause activation of the TLR4 Radical Cycle and thus be associated with the onset of chronic inflammatory and O&NS illnesses, such as CFS, in some vulnerable individuals. Cinnamon, an antagonist of the TLR4 complex, and Hydrogen, a potent antiinflammatory and oxygen radical scavenger, may have efficacy treating LP&P-induced illness.
Assuntos
Hiper-Reatividade Brônquica , Cinnamomum zeylanicum , Processos de Cópia , Síndrome de Fadiga Crônica , Hidrogênio/uso terapêutico , Impressão/instrumentação , Hiper-Reatividade Brônquica/tratamento farmacológico , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/metabolismo , Síndrome de Fadiga Crônica/tratamento farmacológico , Síndrome de Fadiga Crônica/etiologia , Síndrome de Fadiga Crônica/metabolismo , Humanos , Lasers/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Preparações de Plantas/uso terapêutico , Receptor 4 Toll-Like/antagonistas & inibidoresRESUMO
BACKGROUND: Increasing evidence points to a potential role for members of the transient receptor potential family of cation channels on several features of asthmatic disease. The cough sensitivity to inhaled capsaicin is known to reflect the reactivity of these airway sensory nerves. OBJECTIVE: The aim was to study, among patients having a positive methacholine provocation and diagnosed with asthma, capsaicin cough sensitivity, sensitivity to methacholine, and levels of exhaled nitric oxide before and after treatment with inhaled steroids, and further, to measure the self-reported impact from environmental irritants. METHODS: Eighteen steroid-naïve patients with a positive methacholine test underwent capsaicin inhalation provocation on two occasions, before and after regular use of inhaled steroids over at least 3 months. Comparisons were made to 21 healthy controls. Sensitivity to methacholine and levels of exhaled nitric oxide were measured before and after the treatment. The participants also answered a validated questionnaire regarding environmental irritants. RESULTS: The patients displayed higher capsaicin cough sensitivity than the controls before the treatment period, but not afterward. Before treatment, capsaicin cough answer correlated significantly with levels of exhaled nitric oxide, but not with methacholine sensitivity. After treatment with inhaled corticosteroids, the capsaicin cough sensitivity and the inflammatory parameters were normalized. In comparison to the control group, the patients reported more affective reactions to and behavioral disruptions induced by environmental irritants. CONCLUSIONS: In steroid-naïve patients with a positive methacholine test, there is a link between that part of the airway inflammation that is reflected by exhaled nitric oxide and that followed by an augmented reactivity of capsaicin-sensitive sensory nerves. This association disappears after steroid treatment.
Assuntos
Corticosteroides/administração & dosagem , Asma/diagnóstico , Asma/tratamento farmacológico , Irritantes/efeitos adversos , Administração por Inalação , Adolescente , Adulto , Asma/imunologia , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Capsaicina , Estudos de Casos e Controles , Intervalos de Confiança , Poluentes Ambientais/efeitos adversos , Feminino , Seguimentos , Humanos , Modelos Lineares , Masculino , Cloreto de Metacolina , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Índice de Gravidade de Doença , Espirometria/métodos , Estatísticas não Paramétricas , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: Ischemia-reperfusion (I/R) of the rat pancreas induces acute pancreatitis with a systemic inflammatory response. Activated inflammatory cells are sequestered in the lung, and the consequent respiratory burst may increase airway reactivity. In this study, we characterized the effect of the antioxidant curcumin on airway hyperreactivity induced by pancreatic I/R. METHODS: Ischemia of the pancreas was induced by clamping the gastroduodenal and the splenic artery for 2 hours followed by reperfusion for 6 hours. The pulmonary function data of Penh, a measurement of airway resistance, were used to show the airway responses to a methacholine challenge. The blood concentration of oxygen radicals, nitric oxide, and tumor necrosis factor-alpha (TNFalpha) were measured after pancreatic I/R. mRNA expressions of inducible nitric oxide synthase (iNOS) and TNFalpha in lung tissues were measured after pancreatic I/R. Pretreatment with curcumin (20 mg/kg) was administered by intraperitoneal injection 2 hours before pancreatic I/R. RESULTS: The protocol resulted in significant elevations of the blood concentrations of amylase, hydroxyl radical, nitric oxide, TNFalpha, and white cells among the I/R group. iNOS and TNFalpha mRNA expressions also significantly increased in lung tissues. Pulmonary function data showed that pancreatic I/R induced significant increases in responses to methacholine challenge: Penh increased significantly in the I/R group when compared with the sham group. Pretreatment with curcumin significantly attenuated the inflammatory, oxidative, and nitrosative responses and lung tissue iNOS and TNFalpha expressions. Curcumin also attenuated airway reactivity to methacholine challenge. CONCLUSIONS: I/R of the pancreas induced systemic inflammatory responses with respiratory burst, nitrosative stress, and hyperresponses in the airways. Curcumin, which has antioxidant and anti-inflammatory effects, significantly attenuated the inflammatory responses and airway hyperreactivity induced by pancreatic I/R.
Assuntos
Hiper-Reatividade Brônquica/tratamento farmacológico , Curcumina/uso terapêutico , Pâncreas/irrigação sanguínea , Traumatismo por Reperfusão/complicações , Amilases/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/fisiopatologia , Masculino , Metilguanidina/sangue , Óxido Nítrico/sangue , Óxido Nítrico Sintase Tipo II/sangue , Óxido Nítrico Sintase Tipo II/genética , Pâncreas/metabolismo , Pâncreas/patologia , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/fisiopatologia , Testes de Função Respiratória , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genéticaRESUMO
OBJECTIVE: This study assessed current health risks due to occupational exposure to coffee dust. METHODS: We performed a cross-sectional study in a coffee haulage company (n = 24), a coffee silo (n = 19), and a decaffeinating company (n = 17). Cross-shift and cross-week case histories of these employees as well as lung function values were recorded. During the handling of green coffee, measurements of airborne dust were conducted. RESULTS: The employees in these workplaces were mainly affected by erythematous and rhinoconjunctival symptoms. They occurred especially in subjects exposed to a high dust load (> 10 mg of inhalable dust per cubic meter of air; n = 28) [Pearson chi(2) test, p = 0.020 and p = 0.023]. IgE antibodies to green coffee and castor beans were detected in 3 workers and 10 workers, respectively. The majority of them (two employees and six employees, respectively) had shown respiratory symptoms during the past 12 months. The preshift lung function values were below average but were not dependent on the level of the inhalable coffee dust exposure. Employees with a coffee dust load > 10 mg/m(3) of air showed higher unspecific bronchial responsiveness more frequently than those with lower exposures. CONCLUSION: During the transshipment (especially during unloading) of green coffee, a high and clinically relevant exposure to irritative and sensitizing dust occurs. Therefore, efforts to reduce these dust exposures are generally recommended.
Assuntos
Hiper-Reatividade Brônquica/etiologia , Café/efeitos adversos , Poeira/imunologia , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Saúde Ocupacional , Adulto , Hiper-Reatividade Brônquica/epidemiologia , Hiper-Reatividade Brônquica/fisiopatologia , Café/imunologia , Estudos Transversais , Monitoramento Ambiental/métodos , Monitoramento Epidemiológico , Feminino , Humanos , Incidência , Exposição por Inalação , Masculino , Concentração Máxima Permitida , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Probabilidade , Testes de Função Respiratória , Medição de Risco , Testes Cutâneos , Estatísticas não ParamétricasRESUMO
Between the upper and the lower respiratory tracts exists a link. Numerous epidemiological, immunological studies and clinical observations suggest the pathogenic unity of the upper and lower airways. The most important observations regarding the nose-lung interaction is rhinitis and asthma. The inflammatory process in the nose is the same as in the bronchi, clinically defined as rhinosinusitis, nasal polyps, asthma, bronchial hyperreactivity, allergy, viral infections. The strict link between the rhinosinusitis and asthma implies new possibility of influencing one of the two complaints by treating the other one with an integrated therapy (pharmacotherapy, endonasal microsurgery).
Assuntos
Asma/etiologia , Asma/prevenção & controle , Brônquios/fisiopatologia , Nariz/fisiopatologia , Sistema Respiratório/fisiopatologia , Rinite/complicações , Rinite/terapia , Asma/fisiopatologia , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/fisiopatologia , Humanos , Rinite/fisiopatologiaRESUMO
OBJECTIVE: To study the relationships between airway responsiveness to methacholine and capsaicin, proximal or distal reflux and the effects of short-term acid inhibition. MATERIAL AND METHODS: Twenty-nine asthmatics, not taking steroids regularly, underwent respiratory symptom measurements, 24-h dual-probe pH monitoring, and challenges with methacholine and capsaicin. Challenges and symptom measurements were repeated after 12 days' omeprazole treatment (20 mg b.i.d.). The results (median and range) were expressed as PD20 methacholine (mg) and PD5 capsaicin (dose causing five coughs, nmol). RESULTS: Seventeen patients presented pathological reflux in the distal esophagus, and 17 in the proximal esophagus. At baseline no correlation was found between PD20 or PD5 and reflux. Treatment with omeprazole did not change bronchial responsiveness to methacholine (basal: 0.16 mg, 0.02-1.27; omeprazole: 0.15 mg, 0.02-1.60); omeprazole decreased the tussive response to capsaicin (basal: 0.08 nmol, 0.08-2.46; omeprazole: 0.61 nmol, 0.08-9.84, p<0.001) only in patients with pathological reflux. The decrease was positively correlated with proximal acid exposure (r2=0.70, p<0.001). Omeprazole reduced asthma symptoms in patients with proximal reflux, cough in those with proximal or distal reflux. CONCLUSIONS: In asthmatics, inhibition of gastric acid secretion does not influence bronchial hyperresponsiveness but decreases tussive sensitivity and this effect is related to proximal reflux.
Assuntos
Analgésicos não Narcóticos , Antiulcerosos/uso terapêutico , Asma/fisiopatologia , Broncoconstritores , Capsaicina , Refluxo Gastroesofágico/tratamento farmacológico , Cloreto de Metacolina , Omeprazol/uso terapêutico , Adulto , Resistência das Vias Respiratórias/efeitos dos fármacos , Asma/etiologia , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/fisiopatologia , Testes de Provocação Brônquica , Broncoconstrição/efeitos dos fármacos , Monitoramento do pH Esofágico , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/fisiopatologia , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The availability of STA-1 in suppressing allergen-induced immunoglobulin E (IgE) synthesis, airway inflammation and hyperreactivity in a murine model was investigated. The mice were intraperitoneally sensitized with Dermatophagoides pteronyssinus group 5 allergen (Der p 5) and orally treated with 300 mg/kg of STA-1 every other day for 14 days. The Der p 5-specific immunologic responses including changes of specific immunoglobulin G and E, cells in the broncholarvage fluid, and airway hyperreactivity were measured when mice received inhalation challenge with Der p 5 after sensitization for 21 days. By comparing with sham-treated groups, the synthesis of Der p 5-specific IgE was downregulated while the influx of eosinophils and neutrophils in the airway were remarkably reduced. In addition, Der p 5-induced airway hyperreactivity also was significantly eliminated by STA-1 treatment. These results showed that STA-1 could effectively suppress the Der p 5-induced allergic reactions, and the availability of STA-1 for the treatment of allergic asthma was demonstrated in this study.
Assuntos
Antígenos de Dermatophagoides/imunologia , Hiper-Reatividade Brônquica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Imunoglobulina E/biossíntese , Inflamação/tratamento farmacológico , Aerossóis , Resistência das Vias Respiratórias , Animais , Especificidade de Anticorpos , Asma/patologia , Hiper-Reatividade Brônquica/etiologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Contagem de Células , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/toxicidade , Feminino , Imunoglobulina G/biossíntese , Inflamação/etiologia , Dose Letal Mediana , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Japanese hop (Hop J) pollen has been considered as one of the major causative pollen allergens in the autumn season. We developed a new Hop J immunotherapy extract in collaboration with Allergopharma (Reinbeck, Germany) and investigated immunologic mechanisms during 3 yr immunotherapy. Twenty patients (13 asthma with rhinitis and 7 hay fever) were enrolled from Ajou University Hospital. Sera were collected before, 1 yr, and 3 yr after the immunotherapy. Changes of serum specific IgE, IgG1, and IgG4 levels to Hop J pollen extracts and serum IL-10, IL-12, TGF-beta1 and soluble CD23 levels were monitored by ELISA. Skin reactivity and airway hyper-responsiveness to methacholine were improved during the study period. Specific IgG1 increased at 1 yr then decreased again at 3 yr, and specific IgG4 levels increased progressively (p<0.05, respectively), whereas total and specific IgE levels showed variable responses with no statistical significance. IL-10, TGF-beta1 and soluble CD23 level began to decrease during first year and then further decreased during next two years with statistical significances. (p<0.05, respectively). In conclusion, these findings suggested the favorable effect of long term immunotherapy with Hop J pollen extracts can be explained by lowered IgE affinity and generation of specific IgG4, which may be mediated by IL-10 and TGF-beta1.
Assuntos
Citocinas/sangue , Dessensibilização Imunológica , Poaceae/imunologia , Pólen/imunologia , Hiper-Reatividade Brônquica/etiologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interleucina-10/sangue , Receptores de IgE/sangue , Fator de Crescimento Transformador beta/sangueRESUMO
Increased arginase I activity is associated with allergic disorders such as asthma. How arginase I contributes to and is regulated by allergic inflammatory processes remains unknown. CD4+ Th2 lymphocytes (Th2 cells) and IL-13 are two crucial immune regulators that use STAT6-dependent pathways to induce allergic airways inflammation and enhanced airways responsiveness to spasmogens (airways hyperresponsiveness (AHR)). This pathway is also used to activate arginase I in isolated cells and in hepatic infection with helminths. In the present study, we show that arginase I expression is also regulated in the lung in a STAT6-dependent manner by Th2-induced allergic inflammation or by IL-13 alone. IL-13-induced expression of arginase I correlated directly with increased synthesis of urea and with reduced synthesis of NO. Expression of arginase I, but not eosinophilia or mucus hypersecretion, temporally correlated with the development, persistence, and resolution of IL-13-induced AHR. Pharmacological supplementation with l-arginine or with NO donors amplified or attenuated IL-13-induced AHR, respectively. Moreover, inducing loss of function of arginase I specifically in the lung by using RNA interference abrogated the development of IL-13-induced AHR. These data suggest an important role for metabolism of l-arginine by arginase I in the modulation of IL-13-induced AHR and identify a potential pathway distal to cytokine receptor interactions for the control of IL-13-mediated bronchoconstriction in asthma.
Assuntos
Arginase/antagonistas & inibidores , Arginase/fisiologia , Hiper-Reatividade Brônquica/etiologia , Interleucina-13/fisiologia , Interferência de RNA , Animais , Arginase/genética , Arginase/metabolismo , Arginina/metabolismo , Asma/etiologia , Asma/metabolismo , Regulação Enzimológica da Expressão Gênica , Pulmão/enzimologia , Pulmão/patologia , Camundongos , Camundongos Knockout , Doadores de Óxido Nítrico/metabolismo , Fator de Transcrição STAT6 , Células Th2RESUMO
Propolis, which has been used widely in folk medicine, has been shown to exhibit various biological activities but its immunoregulatory and anti-inflammatory activities in intact animals have not been well studied. We investigated these activities of propolis using an ovalbumin-induced asthma animal model. Mice were immunized and sensitized by exposure to ovalbumin (OVA) antigen and administered with low- (65 mg/kg body weight) and high-dose (325 mg/kg body weight) propolis water extracts by tube feeding. The serum OVA-specific IgE titer and cytokine profiles in cultured splenocytes and bronchoalveolar lavage fluids (BALF) were analyzed. The number of eosinophils in BALF was counted. Here we demonstrate that propolis extracts can suppress the serum levels of OVA-specific IgE and IgG(1), and airway hyperresponsiveness (AHR) in OVA-sensitized mice. There are no significant differences in the concentration of eotaxin or the number of eosinophils in BALF among the four groups. However, the higher dose of propolis extracts decreases the level of IL-5 in BALF. The splenocytes from mice administered with propolis extracts (low- and high-dose groups) exhibit a strong inhibition of IL-10 secretion and up-regulation of IFN-gamma secretion in splenocytes stimulated with concanavalin A (ConA). In addition, cytokine (IFN-gamma, IL-6, and IL-10) secretion in OVA-stimulated splenocytes from the propolis groups was significantly lower than that in the control group. These results suggest that propolis extracts may be a potential novel therapeutic agent for asthma.
Assuntos
Asma/prevenção & controle , Pneumonia/prevenção & controle , Própole/farmacologia , Animais , Asma/etiologia , Asma/imunologia , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/prevenção & controle , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Quimiocina CCL11 , Quimiocinas CC/análise , Quimiocinas CC/imunologia , Citocinas/análise , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Contagem de Leucócitos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Pneumonia/etiologia , Pneumonia/imunologia , Própole/química , Baço/citologia , Baço/imunologiaAssuntos
Asma/etiologia , Hiper-Reatividade Brônquica/etiologia , Doenças Profissionais/etiologia , Panax/efeitos adversos , Rinite Alérgica Perene/etiologia , Adulto , Asma/diagnóstico , Hiper-Reatividade Brônquica/diagnóstico , Testes de Provocação Brônquica , Poeira/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Immunoblotting , Imunoglobulina E/imunologia , Coreia (Geográfico) , Doenças Profissionais/diagnóstico , Exposição Ocupacional/efeitos adversos , Panax/imunologia , Rinite Alérgica Perene/diagnóstico , Medição de Risco , Testes CutâneosRESUMO
Japanese hop (Hop J) pollen has been considered as one of the major causative pollen allergens in the autumn season. We developed a new Hop J immunotherapy extract in collaboration with Allergopharma (Reinbeck, Germany) and investigated immunologic mechanisms during 3 yr immunotherapy. Twenty patients (13 asthma with rhinitis and 7 hay fever) were enrolled from Ajou University Hospital. Sera were collected before, 1 yr, and 3 yr after the immunotherapy. Changes of serum specific IgE, IgG1 , and IgG4 levels to Hop J pollen extracts and serum IL-10, IL-12, TGF-beta1 and soluble CD23 levels were monitored by ELISA. Skin reactivity and airway hyper-responsiveness to methacholine were improved during the study period. Specific IgG1 increased at 1 yr then decreased again at 3 yr, and specific IgG4 levels increased progressively (p<0.05, respectively), whereas total and specific IgE levels showed variable responses with no statistical significance. IL-10, TGF-beta1 and soluble CD23 level began to decrease during first year and then further decreased during next two years with statistical significances. (p<0.05, respectively). In con-clusion, these findings suggested the favorable effect of long term immunotherapy with Hop J pollen extracts can be explained by lowered IgE affinity and generation of specific IgG4 , which may be mediated by IL-10 and TGF-beta1.
Assuntos
Humanos , Fator de Crescimento Transformador beta/sangue , Receptores de IgE/sangue , Pólen/imunologia , Poaceae/imunologia , Interleucina-10/sangue , Imunoglobulina G/sangue , Imunoglobulina E/sangue , Dessensibilização Imunológica , Citocinas/sangue , Hiper-Reatividade Brônquica/etiologiaRESUMO
Asthma prevalence continues to increase despite the progress that has been made in the treatment options for asthma. Alternative treatment therapies that reduce the dose requirements of pharmacological interventions would be beneficial, and could potentially reduce the public health burden of this disease. There is accumulating evidence that dietary modification has potential to influence the severity of asthma and reduce the prevalence and incidence of this condition. A possible contributing factor to the increased incidence of asthma in Western societies may the consumption of a pro-inflammatory diet. In the typical Western diet, 20-25-fold more omega (n)-6 polyunsaturated fatty acids (PUFA) than n-3 PUFA are consumed, which results in the release of pro-inflammatory arachidonic acid metabolites. Eicosapentaenoic acid and docosahexaenoic acid are n-3 PUFA derived from fish oil that competitively inhibit n-6 PUFA arachidonic acid (AA) metabolism and this reduce the generation of pro-inflammatory 4-series leukotrienes (LTs) and 2-series prostaglandins (PGs) and production of cytokines from inflammatory cells. These data are consistent with the proposed pathway by which dietary intake of n-3 PUFA modulates lung disease. This article will review the existing information concerning the relationship between n-3 PUFA supplementation and airway hyperresponsiveness in asthma. It includes studies assessing the efficacy of n-3 PUFA supplementation in exercise-induced bronchoconstriction. This review will also address the question as to whether supplementing the diet with n-3 PUFA represents a viable alternative treatment regimen for asthma.
Assuntos
Asma/complicações , Hiper-Reatividade Brônquica/dietoterapia , Hiper-Reatividade Brônquica/etiologia , Suplementos Nutricionais , Ácidos Graxos Ômega-3/uso terapêutico , HumanosRESUMO
BACKGROUND: Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year. METHODS: House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation. RESULTS: Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling. CONCLUSIONS: Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.
Assuntos
Asma/imunologia , Asma/fisiopatologia , Cynodon/imunologia , Modelos Animais de Doenças , Hipersensibilidade/imunologia , Pyroglyphidae/imunologia , Animais , Asma/complicações , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/imunologia , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/imunologia , Gatos , Citocinas/biossíntese , Ensaio de Imunoadsorção Enzimática , Eosinofilia/etiologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/fisiopatologia , Imunoglobulina A/análise , Imunoglobulina E/sangue , Imunoglobulina G/análise , Pulmão/imunologia , Pulmão/patologia , Ativação Linfocitária/imunologia , Linfócitos/imunologiaAssuntos
Asma/tratamento farmacológico , Brônquios/efeitos dos fármacos , Hiper-Reatividade Brônquica/tratamento farmacológico , Glucocorticoides/uso terapêutico , Estações do Ano , Triancinolona Acetonida/uso terapêutico , Alérgenos/efeitos adversos , Asma/etiologia , Asma/fisiopatologia , Proteínas Sanguíneas/metabolismo , Brônquios/metabolismo , Brônquios/fisiopatologia , Hiper-Reatividade Brônquica/etiologia , Hiper-Reatividade Brônquica/fisiopatologia , Proteínas Granulares de Eosinófilos , Eosinófilos/metabolismo , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Pólen/efeitos adversos , Ribonucleases/metabolismoRESUMO
OBJECTIVE: Many patients with allergic rhinitis (AR) have bronchial hyper-responsiveness (BHR), and seasonal variation of BHR has been demonstrated in these patients. We aimed to investigate how BHR in children with seasonal AR is modified by triamcinolone acetonide aqueous nasal spray (TANS) therapy during the pollen season. A secondary aim was to assess the efficacy of TANS on nasal congestion by acoustic rhinometry and symptom scores. METHODS: A total of 34 children aged 7-18 years with grass pollen-induced AR and 18 age and sex-matched healthy controls were included in study. The patients were divided into the following two subgroups: 22 patients who had AR only; and 12 patients who had AR and asthma. All of them had a baseline BHR (PC20FEV1 methacholine < 8mg/ml). All patients received 220 microg TANS once daily for 4 weeks following a 1-week run-in period. Nasal patency was measured by acoustic rhinometry and patients recorded their nasal obstruction scores in a diary. RESULTS: There was no significant difference at baseline pulmonary function test parameters between the patients and the healthy control children. None of the control subjects had BHR. Asthmatic children with AR had significantly reduced baseline PC20FEV1 when compared with the AR only group [mean +/- S.E.M., (1.60 +/- 0.57 mg/ml versus 2.93 +/- 0.42 mg/ml, P = 0.021)]. The mean PC20FEV1 values increased slightly at the end of treatment in both group (from 1.60 +/- 0.57 mg/ml to 3.25 +/- 1.11 and from 2.93 +/- 0.42 mg/ml to 3.93 +/- 1.41 mg/ml), but the change was not statistically significant. TANS produced substantial symptomatic recovery in nasal obstruction according to patients' daily diary assessments, and significantly improved all objective acoustic rhinometry parameters. CONCLUSIONS: Once-daily intranasal TANS 220 microg effectively controlled nasal obstruction in children with seasonal AR according to subjective and objective assessments, and blocked the increase in BHR to methacholine after high-load natural pollen exposure. There was no correlation between patients' own subjective assessment of nasal obstruction and objective acoustic rhinometric assessment.
Assuntos
Hiper-Reatividade Brônquica/tratamento farmacológico , Imunossupressores/uso terapêutico , Obstrução Nasal/tratamento farmacológico , Rinite Alérgica Sazonal/tratamento farmacológico , Triancinolona Acetonida/uso terapêutico , Administração Intranasal , Adolescente , Alérgenos/efeitos adversos , Asma/complicações , Asma/tratamento farmacológico , Asma/fisiopatologia , Hiper-Reatividade Brônquica/etiologia , Broncoconstritores , Estudos de Casos e Controles , Criança , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Cloreto de Metacolina , Obstrução Nasal/fisiopatologia , Pólen/efeitos adversos , Testes de Função Respiratória , Rinite Alérgica Sazonal/complicações , Rinite Alérgica Sazonal/fisiopatologia , Rinometria Acústica , Espirometria , Triancinolona Acetonida/administração & dosagemRESUMO
BACKGROUND: Recent evidence suggests that patients with allergic rhinitis have lower airway inflammation and a higher prevalence of bronchial hyperresponsiveness (BHR) regardless of asthma. OBJECTIVE: To investigate markers of lower airway inflammation in nonasthmatic children with seasonal allergic rhinitis (SAR) before and during pollen season and the effect of nasal triamcinolone acetonide on seasonal variations in these parameters. METHODS: Thirty-two nonasthmatic children with SAR in response to grass and/or weed pollens were recruited and separated into 2 groups. Group 1 was treated with triamcinolone acetonide (220 microg once daily) for 6 weeks, and group 2 received no intranasal corticosteroid treatment. Bronchial responsiveness to methacholine [concentration that caused a decrease in forced expiratory volume in 1 second of 20% (PC20)], eosinophil counts in sputum and peripheral blood, and eosinophil cationic protein (ECP) levels in sputum and serum were measured before and during grass pollen season. RESULTS: Twenty-eight patients completed the study. During the pollen season, methacholine PC20 significantly decreased in both groups when compared with the corresponding preseasonal values (P = .01 and P = .003, respectively). The mean percentage of sputum eosinophils increased significantly during the pollen season compared with preseasonal values in group 1 and group 2 (12.7% +/- 2.1% vs 16.5% +/- 2.1%, P = .007, and 11.0% +/- 2.0% vs 20.2% +/- 1.4%, P = .003, respectively). Median [interquartile ranges (IQR)] sputum ECP levels were significantly higher during the pollen season when compared with the preseasonal values in group 1 and group 2 [7.5 microg/L (3.5-36.0 microg/L) vs 35.5 microg/L (13.0-71.7 microg/L), P = .04, and 18.0 microg/L (6.0-36.0 microg/L) vs 69.0 microg/L (39.0-195.0 microg/L), P = .003, respectively], as were the serum ECP levels [6.0 microg/L (2.0-13.0 microg/L) vs 19.0 microg/L (14.0-43.5 microg/L), P = .004, and 6.0 microg/L (3.0-7.0 microg/L) vs 18.0 microg/L (6.0-36.0 microg/L), P = .001, respectively]. Although the mean number of eosinophils in blood increased during the pollen season in both groups, it was only significant in group 2 (70.0 +/- 20.0 vs 161.6 +/- 29.0, P = .02). CONCLUSIONS: Although prophylactic nasal corticosteroid treatment provides significant reduction of nasal symptoms and rescue antihistamine use, there is no significant prevention in the seasonal increase of bronchial inflammation and methacholine BHR.