RESUMO
Interleukin-5 (IL-5) is important in the control of differentiation, migration, and activation of eosinophils. In order to study the role of IL-5 in the development of eosinophilic inflammation of the airways, we have used a monoclonal antibody to murine IL-5 (TRFK-5) in a murine model of allergic pulmonary inflammation. B6D2F1 mice were sensitized with alum-precipitated ovalbumin and were challenged with aerosolized ovalbumin on day 12 after sensitization. Samples of bronchoalveolar lavage (BAL) fluid, lung tissue, blood, and bone marrow aspirate were collected at different times after ovalbumin challenge. Twenty-four hours after challenge there were significant increases in the number of eosinophils in the BAL fluid, lung tissue, and blood while bone marrow eosinophils were decreased. Treatment of sensitized mice with TRFK-5 (0.01-1 mg/kg, i.p.) 2 h before ovalbumin challenge reduced the numbers of eosinophils in the BAL fluid and lung tissue and prevented the decrease in bone marrow eosinophils in a dose-dependent fashion. The number of eosinophils in the BAL fluid, peribronchial and alveolar regions of the lung was also reduced when TRFK-5 (2 mg/kg, i.p.) was given up to 5 d after ovalbumin challenge. Furthermore, there was no evidence of increased epithelial damage, edema, or the presence of mucus that could have resulted from eosinophil apoptosis and release of toxic proteins after neutralization of IL-5. These results demonstrate an important role for IL-5 in the development of eosinophilic inflammation of the airways and for the migration of eosinophils from the bone marrow into blood in response to antigen challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Inflamação/metabolismo , Interleucina-5/análise , Pneumopatias/metabolismo , Albuminas/administração & dosagem , Albuminas/imunologia , Animais , Anticorpos/uso terapêutico , Modelos Animais de Doenças , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Hipersensibilidade/prevenção & controle , Inflamação/imunologia , Inflamação/prevenção & controle , Interleucina-5/imunologia , Pneumopatias/etiologia , Pneumopatias/imunologia , Pneumopatias/terapia , CamundongosAssuntos
Hipersensibilidade/terapia , Interferon gama/uso terapêutico , Interleucina-4/imunologia , Interleucina-5/imunologia , Eosinofilia Pulmonar/terapia , Animais , Medula Óssea/imunologia , Imunoterapia , Interferons , Camundongos , Camundongos Endogâmicos , Ovalbumina/imunologia , Eosinofilia Pulmonar/patologia , Proteínas RecombinantesRESUMO
Mast cells are important effector cells in IgE-mediated acute allergic reactions. Mast cells also produce cytokines such as interleukin (IL)-3, IL-4, IL-5, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) that regulate the function of eosinophils and the development of a late-phase inflammatory response to antigen challenge. To evaluate the role of mast cells on the development of IgE-mediated allergic pulmonary eosinophilia in vivo, we compared the eosinophil infiltration into lungs of mast cell deficient mice (WBB6F1/J-W/Wv) with their congenic normal littermates (W/W+). Mice were sensitized with alum-precipitated ovalbumin and challenged with aerosolized ovalbumin on day 12 after sensitization. Bronchoalveolar lavage (BAL) fluid, lung tissue biopsies, and blood samples were collected after ovalbumin challenge. Eosinophil numbers in the BAL and lung tissue, lung eosinophil peroxidase (EPO) activity and serum levels of IgE and IgG1 were measured. In sensitized W/W+ mice, there were increased numbers of eosinophils in the BAL fluid and lung tissue, and EPO levels were increased after ovalbumin challenge. Ovalbumin challenge of sensitized mast-cell-deficient mice produced fewer numbers of eosinophils in the BAL fluid and lungs, and EPO levels were also reduced compared with their challenged congenic littermates. On the other hand, levels of serum IgE and IgG1 were not different between W/Wv mice and their congenic littermates.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Eosinófilos/imunologia , Hipersensibilidade/imunologia , Mastócitos/imunologia , Pneumonia/imunologia , Animais , Células da Medula Óssea , Testes de Provocação Brônquica , Líquido da Lavagem Broncoalveolar/citologia , Movimento Celular , Peroxidase de Eosinófilo , Imunização Passiva , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Masculino , Camundongos , Camundongos Mutantes , Ovalbumina , Peroxidases/metabolismoAssuntos
Citocinas/fisiologia , Glucocorticoides/uso terapêutico , Eosinofilia Pulmonar/imunologia , Hipersensibilidade Respiratória/imunologia , Animais , Antígenos/imunologia , Transplante de Medula Óssea , Líquido da Lavagem Broncoalveolar/citologia , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Interleucina-5/fisiologia , Mastócitos/fisiologia , Camundongos , Camundongos Endogâmicos , Eosinofilia Pulmonar/tratamento farmacológico , Hipersensibilidade Respiratória/tratamento farmacológicoRESUMO
Based on its involvement in eosinophil biology, interleukin 5 (IL-5) may play a role in the pulmonary eosinophilia associated with allergic reactions. We have examined that hypothesis using a neutralizing antibody to IL-5 in ovalbumin-sensitized guinea pigs challenged with aerosolized antigen. The extent of eosinophilia has been quantitated in bronchoalveolar lavage (BAL) and by histologic evaluation of lung tissue sections. Acute intraperitoneal administration of a rat IgG, monoclonal antibody to murine IL-5 derived from TRFK-5 cells prevented lung and BAL eosinophilia in a dose-dependent fashion at and above 10 micrograms per guinea pig. Treatment with either an experimentally irrelevant, isotype-matched antibody from GL113 cells or with heat-denatured IL-5 antibody was without effect. These studies demonstrate the importance of IL-5 to pulmonary eosinophilia in challenged, allergic guinea pigs.