Infliximab alleviates inflammation and ex vivo airway hyperreactivity in asthmatic E3 rats
Tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of asthma, and neutralization of TNF-α is an effective therapy for inflammatory diseases. The present study tested the idea that a TNF-α antibody, infliximab, may be useful in the management of asthma. E3 rats were immunized wit...
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Veröffentlicht in: | International immunology 2011-07, Vol.23 (7), p.443-451 |
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Sprache: | eng |
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Zusammenfassung: | Tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of asthma, and neutralization of TNF-α is an effective therapy for inflammatory diseases. The present study tested the idea that a TNF-α antibody, infliximab, may be useful in the management of asthma. E3 rats were immunized with ovalbumin (OVA)/alum and received infliximab intra-peritoneally. Two weeks later, OVA-PBS was instilled intranasally daily for 7 days. Bronchoalveolar lavage fluids (BALFs), serum and lung homogenates were collected for analysis of cells and inflammatory mediators. Contractile responses of lobar-bronchus segments to agonists were functionally tested. Pulmonary tissues were investigated using histological examination. The results showed that the sensitized 'model E3 rats' exhibited an increase in the total amount of inflammatory cells, primarily eosinophils, in BALF and pulmonary tissue, as well as epithelial damage. Serum levels of IgE increased and so did the levels of nitric oxide, inducible nitric oxide synthase, TNF-α and IL-4, IL-5 and IL-13 in lung homogenate and serum. Furthermore, the contractile responses in bronchi induced by endothelin-1, sarafotoxin 6c and bradykinin increased and isoprenaline-induced relaxations decreased. All these changes induced by the sensitization procedure were reduced by the infliximab treatment. The results suggest that infliximab prevents the development of local airway inflammation and antagonizes changes of the bronchial smooth muscle receptor phenotype, thereby blocking the development of airway smooth muscle hyperreactivity of asthmatic rats. |
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ISSN: | 0953-8178 1460-2377 1460-2377 |
DOI: | 10.1093/intimm/dxr032 |