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Infliximab alleviates inflammation and ex vivo airway hyperreactivity in asthmatic E3 rats

Cai, Yan; Cao, Yong-Xiao; Lu, She-Min; Xu, Cang-Bao LU and Cardell, Lars Olaf (2011) In International Immunology 23(7). p.443-451
Abstract
Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of asthma, and neutralization of TNF-alpha is an effective therapy for inflammatory diseases. The present study tested the idea that a TNF-alpha 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... (More)
Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of asthma, and neutralization of TNF-alpha is an effective therapy for inflammatory diseases. The present study tested the idea that a TNF-alpha 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-alpha 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
asthma, cytokine, inflammation, receptor, tumor necrosis factor-alpha
in
International Immunology
volume
23
issue
7
pages
443 - 451
publisher
Oxford University Press
external identifiers
  • wos:000292315400005
  • scopus:79960068925
ISSN
1460-2377
DOI
10.1093/intimm/dxr032
language
English
LU publication?
yes
id
5d6cbb33-b77a-434e-8751-45640511c66a (old id 2032274)
date added to LUP
2011-08-02 08:57:37
date last changed
2017-11-12 03:14:36
@article{5d6cbb33-b77a-434e-8751-45640511c66a,
  abstract     = {Tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of asthma, and neutralization of TNF-alpha is an effective therapy for inflammatory diseases. The present study tested the idea that a TNF-alpha 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-alpha 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.},
  author       = {Cai, Yan and Cao, Yong-Xiao and Lu, She-Min and Xu, Cang-Bao and Cardell, Lars Olaf},
  issn         = {1460-2377},
  keyword      = {asthma,cytokine,inflammation,receptor,tumor necrosis factor-alpha},
  language     = {eng},
  number       = {7},
  pages        = {443--451},
  publisher    = {Oxford University Press},
  series       = {International Immunology},
  title        = {Infliximab alleviates inflammation and ex vivo airway hyperreactivity in asthmatic E3 rats},
  url          = {http://dx.doi.org/10.1093/intimm/dxr032},
  volume       = {23},
  year         = {2011},
}