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Int Arch Allergy Immunol ; 140(3): 261-9, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16699287

RESUMO

BACKGROUND: Recombinant allergen-specific immunoglobulin G (IgG) antibody therapy can reduce allergic asthma symptoms by inhibiting the immunoglobulin E (IgE)-mediated allergic response. This study investigated the effect of intranasally administered allergen-specific monoclonal (mAb) and polyclonal (pAb) antibody on airway inflammation and hyperresponsiveness (AHR) in a mouse model of human asthma. METHODS: Ovalbumin (OVA)-specific IgG2b antibodies were generated by phage display using spleens from OVA-immunized mice, and screening against OVA and finally expressed in CHO cells. Sensitized mice were treated intranasally with either a recombinant anti-OVA mAb (gc32) or a polyclonal preparation comprising seven selected antibodies (including gc32). Control mice received diluent only, OVA only, a control polymeric IgG or dexamethasone. Following challenge with nebulized OVA, investigators assessed airway inflammation by histology and cellular composition of the bronchoalveolar fluid, and methacholine-induced airway hyperresponsiveness (AHR). Serum levels of total and OVA-specific IgE were measured by ELISA. RESULTS: Sensitized mice developed airway inflammation and AHR in response to OVA challenge. Intranasally administered OVA-specific murine polyclonal or monoclonal IgG2b antibodies both reduced OVA-induced lung inflammation. Polyclonal, but not anti-OVA mAb, also reduced AHR and eosinophil influx into the airway lumen. Both anti-OVA antibody preparations reduced levels of specific IgE with no effect on total IgE levels. CONCLUSIONS: Intranasal treatment with allergen-specific pAb reduces pulmonary inflammation and AHR in a mouse model of allergic asthma, but allergen-specific mAb reduces inflammation only. Allergen-specific recombinant pAb offers a potentially valuable therapeutic approach to the management of allergic asthma.


Assuntos
Anticorpos/uso terapêutico , Asma/imunologia , Asma/terapia , Imunoterapia/métodos , Administração Intranasal , Animais , Anticorpos/administração & dosagem , Anticorpos/imunologia , Especificidade de Anticorpos , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Histocitoquímica , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/prevenção & controle , Imunoglobulina E/sangue , Imunoterapia/normas , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico
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