ABSTRACT
Recent studies emphasize the presence of alveolar tissue inflammation in asthma. Immunotherapy has been considered a possible therapeutic strategy for asthma, and its effect on lung tissue had not been previously investigated. Measurements of lung tissue resistance and elastance were obtained before and after both ovalbumin and acetylcholine challenges. Using morphometry, we assessed eosinophil and smooth muscle cell density, as well as collagen and elastic fiber content, in lung tissue from guinea pigs with chronic pulmonary allergic inflammation. Animals received seven inhalations of ovalbumin (1-5 mg/ml; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). The ovalbumin-exposed animals presented an increase in baseline and in postchallenge resistance and elastance related to baseline, eosinophil density, and collagen and elastic fiber content in lung tissue compared with controls. Baseline and post-ovalbumin and acetylcholine elastance and resistance, eosinophil density, and collagen and elastic fiber content were attenuated in OT1 and OT2 groups compared with the OVA group. Our results show that inducing oral tolerance attenuates lung tissue mechanics, as well as eosinophilic inflammation and extracellular matrix remodeling induced by chronic inflammation.
Subject(s)
Airway Resistance , Asthma/immunology , Extracellular Matrix/metabolism , Immune Tolerance , Lung Compliance , Lung/immunology , Pneumonia/immunology , Pulmonary Eosinophilia/immunology , Administration, Inhalation , Administration, Oral , Animals , Asthma/metabolism , Asthma/physiopathology , Chronic Disease , Collagen/metabolism , Disease Models, Animal , Elastic Tissue/metabolism , Guinea Pigs , Lung/metabolism , Lung/pathology , Lung/physiopathology , Ovalbumin/administration & dosage , Pneumonia/metabolism , Pneumonia/physiopathology , Pulmonary Eosinophilia/metabolism , Pulmonary Eosinophilia/physiopathology , Pulmonary Eosinophilia/prevention & control , Time FactorsABSTRACT
Enhanced respiratory syncytial virus disease, a serious pulmonary disorder that affected recipients of an inactivated vaccine against respiratory syncytial virus in the 1960s, has delayed the development of vaccines against the virus. The enhanced disease was characterized by immune complex-mediated airway hyperreactivity and a severe pneumonia associated with pulmonary eosinophilia. In this paper, we show that complement factors contribute to enhanced-disease phenotypes. Mice with a targeted disruption of complement component C5 affected by the enhanced disease displayed enhanced airway reactivity, lung eosinophilia, and mucus production compared to wild-type mice and C5-deficient mice reconstituted with C5. C3aR expression in bronchial epithelial and smooth muscle cells in the lungs of C5-deficient mice was enhanced compared to that in wild-type and reconstituted rodents. Treatment of C5-deficient mice with a C3aR antagonist significantly attenuated airway reactivity, eosinophilia, and mucus production. These results indicate that C5 plays a crucial role in modulating the enhanced-disease phenotype, by affecting expression of C3aR in the lungs. These findings reveal a novel autoregulatory mechanism for the complement cascade that affects the innate and adaptive immune responses.
Subject(s)
Bronchial Hyperreactivity/immunology , Complement C5/metabolism , Membrane Proteins/metabolism , Pulmonary Eosinophilia/immunology , Receptors, Complement/metabolism , Respiratory Syncytial Virus Infections/physiopathology , Respiratory Syncytial Virus, Human/pathogenicity , Animals , Bronchial Hyperreactivity/physiopathology , Bronchial Hyperreactivity/virology , Complement C3a/metabolism , Complement C5/deficiency , Down-Regulation , Membrane Proteins/deficiency , Mice , Pneumonia, Viral/immunology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/virology , Pulmonary Eosinophilia/physiopathology , Pulmonary Eosinophilia/virology , Receptors, Complement/deficiency , Respiratory Syncytial Virus Infections/immunology , Respiratory Syncytial Virus Infections/virology , Severity of Illness IndexABSTRACT
New therapeutic approaches for the treatment of allergic diseases can be aided by the development of agents capable of regulating eosinophilic leukocytes. Here, we evaluated the anti-allergic properties of a crude extract of the Brazilian bromeliaceae Nidularium procerum, focusing on its effects on allergic eosinophilia. By studying allergic pleurisy in actively sensitized C57Bl/6 mice, we observed that pretreatment with N. procerum (2 mg/kg; i.p.) reduced pleural eosinophil influx triggered by allergen challenge. N. procerum was also able to reduce lipid body numbers found within infiltrating eosinophils, indicating that N. procerum in vivo is able to affect both migration and activation of eosinophils. Consistently, pretreatment with N. procerum blocked pleural eosinophil influx triggered by PAF or eotaxin, key mediators of the development of allergic pleural eosinophilia. The effect of N. procerum was not restricted to eosinophils, since N. procerum also inhibited pleural neutrophil and mononuclear cell influx. Of note, N. procerum failed to alter the acute allergic reaction, characterized by mast cell degranulation, oedema, and cysteinyl leukotriene release. N. procerum also had direct effects on murine eosinophils, since it inhibited both PAF- and eotaxin-induced eosinophil chemotaxis on an in vitro chemotactic assay. Therefore, N. procerum may be a promising anti-allergic therapy, inasmuch as it presents potent anti-eosinophil activity.
Subject(s)
Anti-Allergic Agents/pharmacology , Bromeliaceae , Cell Movement/drug effects , Eosinophils/drug effects , Plant Extracts/pharmacology , Pulmonary Eosinophilia/prevention & control , Animals , Asthma/chemically induced , Asthma/physiopathology , Asthma/prevention & control , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cells, Cultured , Chemokine CCL11 , Chemokines, CC/metabolism , Chemokines, CC/pharmacology , Disease Models, Animal , Dose-Response Relationship, Drug , Eosinophils/metabolism , Female , Inclusion Bodies/drug effects , Inclusion Bodies/metabolism , Inflammation Mediators/pharmacology , Interleukin-13/metabolism , Lipid Metabolism/drug effects , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Ovalbumin , Plant Leaves , Platelet Activating Factor/analogs & derivatives , Platelet Activating Factor/pharmacology , Pleurisy/chemically induced , Pleurisy/physiopathology , Pleurisy/prevention & control , Pulmonary Eosinophilia/chemically induced , Pulmonary Eosinophilia/physiopathology , Spleen/cytology , Spleen/drug effects , Spleen/metabolism , Time FactorsABSTRACT
Agonista de receptor b2-adrenérgico pode apresentar efeito imunomodulador. Estudamos a influência do salbutamol sobre a inflamação pulmonar crônica induzida por ovoalbumina em camundongos Balb/c, nos regimes a cada 96 horas (IS) e no regime diário (DS). Houve aumento expressivo de eosinófilos e neutrófilos no lavado broncoalveolar no modelo, a qual foi reduzida após DS. A OVA aumentou a quantidade de células LMN e EPO+ na parede de vias aéreas e no parênquima pulmonar / Beta2-adrenergic receptor agonist showed a imunomodulator effects. We study the influence of intermittent (IS) and diary (DS) regimen of salbutamol on ovalbumin induced chronic lung inflammation. Expressive increasing of eosinophils and neutrophils were observed in bronchoalveolar lavage from our model...
Subject(s)
Animals , Male , Mice , Ovalbumin/immunology , Albuterol/therapeutic use , Pulmonary Eosinophilia/physiopathology , Inflammation/physiopathology , Bronchoalveolar Lavage Fluid/cytology , Mice, Inbred BALB CABSTRACT
Las enfermedades pulmonares eosinofílicas constituyen un variado grupo de patologías que tienen en común la presencia de eosinofilia periférica y tisular e infiltrados radiológicos. Dentro de este grupo se encuentran las neumonías eosinofílicas crónicas. Presentamos dos casos de esta patología en los cuales la biopsia pulmonar no fue necesaria para su diagnóstico. Ambos casos de sexo masculino consultan por síndrome febril y tos, con eosinofilia periférica y eritrosedimentación elevada. En la radiografía y tomografía computada de tórax se observan infiltrados intersticioalveolares periféricos y bilaterales. Examen parasitológico normal. El lavado bronquioalveolar es negativo para células neoplásicas, gérmenes comunes, micológico y tuberculosis, con aumento de Eosinófilos en el mismo. Presentan mejoría clínica y radiológica al tratamiento con corticoides. Actualmente es posible diagnosticar esta patología en base a la presentación clínica típica, los infiltrados radiológicos característicos, el aumento de porcentajes de Eosinófilos en el lavado bronquioalveolar y la rápida respuesta al tratamiento con corticoides, reservando la biopsia pulmonar para casos más dificultosos. (AU)
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/physiopathology , Pulmonary Eosinophilia/diagnostic imaging , Chronic Disease , Adrenal Cortex Hormones/therapeutic use , Pulmonary Eosinophilia/therapy , Fever/complications , Asthma/complications , Bronchoalveolar Lavage/statistics & numerical dataABSTRACT
Las enfermedades pulmonares eosinofílicas constituyen un variado grupo de patologías que tienen en común la presencia de eosinofilia periférica y tisular e infiltrados radiológicos. Dentro de este grupo se encuentran las neumonías eosinofílicas crónicas. Presentamos dos casos de esta patología en los cuales la biopsia pulmonar no fue necesaria para su diagnóstico. Ambos casos de sexo masculino consultan por síndrome febril y tos, con eosinofilia periférica y eritrosedimentación elevada. En la radiografía y tomografía computada de tórax se observan infiltrados intersticioalveolares periféricos y bilaterales. Examen parasitológico normal. El lavado bronquioalveolar es negativo para células neoplásicas, gérmenes comunes, micológico y tuberculosis, con aumento de Eosinófilos en el mismo. Presentan mejoría clínica y radiológica al tratamiento con corticoides. Actualmente es posible diagnosticar esta patología en base a la presentación clínica típica, los infiltrados radiológicos característicos, el aumento de porcentajes de Eosinófilos en el lavado bronquioalveolar y la rápida respuesta al tratamiento con corticoides, reservando la biopsia pulmonar para casos más dificultosos.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/physiopathology , Pulmonary Eosinophilia , Adrenal Cortex Hormones/therapeutic use , Chronic Disease , Pulmonary Eosinophilia/therapy , Asthma/complications , Bronchoalveolar Lavage , Fever/complicationsABSTRACT
Eosinophils play a central role in the establishment and outcome of bronchial inflammation in asthma. Animal models of allergy are useful to answer questions related to mechanisms of allergic inflammation. We have used models of sensitized and boosted guinea pigs to investigate the nature of bronchial inflammation in allergic conditions. These animals develop marked bronchial infiltration composed mainly of CD4+ T-lymphocytes and eosinophils. Further provocation with antigen leads to degranulation of eosinophils and ulceration of the bronchial mucosa. Eosinophils are the first cells to increase in number in the mucosa after antigen challenge and depend on the expression of alpha4 integrin to adhere to the vascular endothelium and transmigrate to the mucosa. Blockage of alpha4 integrin expression with specific antibody prevent not only the transmigration of eosinophils but also the development of bronchial hyperresponsiveness (BHR) to agonists in sensitized and challenged animals, clearly suggesting a role for this cell type in this altered functional site. Moreover, introduction of antibody against Major Basic Protein into the airways also prevents the development of BHR in similar model. BHR can also be suppressed by the use of FK506, an immunosuppressor that reduces in almost 100 per cent the infiltration of eosinophils into the bronchi of allergic animals. These data support the concept that eosinophil is the most important pro-inflammatory factor in bronchial inflammation associated with allergy.
Subject(s)
Animals , Guinea Pigs , Asthma/physiopathology , Bronchitis , Eosinophils/physiology , Pulmonary Eosinophilia/physiopathology , Respiratory Hypersensitivity , Integrins , TacrolimusABSTRACT
La Enfermedad Pulmonar Eosinófila es producida por diferentes patologías, en las cuales hay un aumento de los eosinófilos tisulares y circulantes. Los mecanismos patogénicos, en la mayoría de las causas están pobremente aclarados. Entre los desórdenes que pueden desencadenarla se encuentran hipersensibilidad a drogas; secundaria a enfermedad parasitaria; micosis; vasculitis y otras enfermedades infecciosas como la tuberculosis. También puede acompañar a neoplasias como carcinoma broncogénico y enfermedad de Hodgkin. Se presenta el caso de un paciente de sexo masculino, de 45 años de edad con SIDA y Tuberculosis Pulmonar, que durante el tratamiento desarrolla eosinofilia periférica e infiltrados fugases (periféricos y bilaterales) en la radiografía de tórax. Se concluye que los pacientes con Sida y Tuberculosis, tienen mayor proporción de reacciones adversas a drogas, y que la Tuberculosis puede desencadenar per se una Eosinofilia Pulmonar Simple o Idiopática.
Subject(s)
Humans , Male , Middle Aged , Pulmonary Eosinophilia/etiology , Pulmonary Eosinophilia/physiopathology , Acquired Immunodeficiency Syndrome/complications , Tuberculosis, Pulmonary/complications , Carcinoma, Bronchogenic/complications , Drug Hypersensitivity , Hodgkin Disease/complications , Mycoses , Rifampin/adverse effects , Sulfasalazine/adverse effectsABSTRACT
La Enfermedad Pulmonar Eosinófila es producida por diferentes patologías, en las cuales hay un aumento de los eosinófilos tisulares y circulantes. Los mecanismos patogénicos, en la mayoría de las causas están pobremente aclarados. Entre los desórdenes que pueden desencadenarla se encuentran hipersensibilidad a drogas; secundaria a enfermedad parasitaria; micosis; vasculitis y otras enfermedades infecciosas como la tuberculosis. También puede acompañar a neoplasias como carcinoma broncogénico y enfermedad de Hodgkin. Se presenta el caso de un paciente de sexo masculino, de 45 años de edad con SIDA y Tuberculosis Pulmonar, que durante el tratamiento desarrolla eosinofilia periférica e infiltrados fugases (periféricos y bilaterales) en la radiografía de tórax. Se concluye que los pacientes con Sida y Tuberculosis, tienen mayor proporción de reacciones adversas a drogas, y que la Tuberculosis puede desencadenar per se una Eosinofilia Pulmonar Simple o Idiopática. (AU)
Subject(s)
Humans , Male , Middle Aged , Acquired Immunodeficiency Syndrome/complications , Pulmonary Eosinophilia/etiology , Pulmonary Eosinophilia/physiopathology , Tuberculosis, Pulmonary/complications , Drug Hypersensitivity , Mycoses , Sulfasalazine/adverse effects , Rifampin/adverse effects , Carcinoma, Bronchogenic/complications , Hodgkin Disease/complicationsABSTRACT
Presentamos el caso de una mujer de 38 años con asma, eosinofilia periférica, sinusitis y opacidades interticiales difusas, bilaterales y fugaces en la radiografía de tórax. El procedimiento diagnóstico fue biopsia pulmonar a cielo abierto donde se encontró una vasculitis eosinofilica características del Síndrome de Churg-Strauss. Comentamos los principales hallazgos clínicos, radiológicos e histopatológicos.
Subject(s)
Humans , Female , Adult , Churg-Strauss Syndrome/surgery , Churg-Strauss Syndrome/classification , Churg-Strauss Syndrome/complications , Churg-Strauss Syndrome/diagnosis , Churg-Strauss Syndrome/epidemiology , Churg-Strauss Syndrome/etiology , Churg-Strauss Syndrome/physiopathology , Churg-Strauss Syndrome/mortality , Churg-Strauss Syndrome/pathology , Churg-Strauss Syndrome/drug therapy , Churg-Strauss Syndrome , Churg-Strauss Syndrome/therapy , Pulmonary Eosinophilia/complications , Pulmonary Eosinophilia/diagnosis , Pulmonary Eosinophilia/drug therapy , Pulmonary Eosinophilia/epidemiology , Pulmonary Eosinophilia/etiology , Pulmonary Eosinophilia/physiopathology , Pulmonary Eosinophilia/surgery , Pulmonary Eosinophilia/therapyABSTRACT
To determine the frequency of renal abnormalities occurring with Bancroftian filarial infections and to assess the effects of treatment on such abnormalities, we initiated a prospective, hospital-based study of 20 microfilaremic and five amicrofilaremic patients with Wuchereria bancrofti infections. Thorough clinical evaluations and detailed renal assessments were made prior to treatment and at multiple time points for 60 days following a standard twelve-day course of treatment with diethylcarbamazine (DEC). There were two important findings. First, even prior to DEC treatment, almost half of the microfilaremic patients had hematuria and/or proteinuria. Second, treatment with DEC induced these same abnormalities in almost all of the remaining microfilaremic patients. However, this DEC-induced hematuria and/or proteinuria was transient, and the long-term response to DEC in all of the microfilaremic patients was resolution of the abnormal renal findings during the two-month followup period. In the amicrofilaremic study patients, no hematuria or proteinuria was detected before, during, or after treatment with DEC.