The role of Tumour Necrosis Factor alpha (TNF-a) in asthma
The role of Tumour Necrosis Factor alpha (TNF-a) in asthma
Allergen challenge induces the proinflammatory cytokines and has been used to study the pathogenic mechanisms in asthma. The study presented in Chapter 3 used a repeated low dose allergen challenge model which is more likely to simulate natural allergen exposure to investigate the effects of allergen on bronchial biopsies from mild allergic asthmatics. Low dose allergen exposure results in up regulation of TNF-α in the bronchial biopsies. This increase was associated with a parallel increase in mast cell numbers suggesting the possible source of TNF-α as the mast cells. This was associated with an associated increase in adhesion molecules ICAM-1 and VCAM-1.
In the ex vivo study on bronchial biopsies of moderately severe asthmatics the results were similar to the low dose allergen exposure where TNF-α levels were increased following exposure to Der p and this was suppressed in the presence of CDP 870- a TNF-α blocking monoclonal antibody. CDP 870 was also able to suppress the levels of IL-8 and adhesion molecules.
Having seen a positive response with CDP 870 we had the opportunity of observing the effects of blocking TNF-α with a soluble fusion protein-p75 receptor (etanercept) on patients with chronic severe corticosteroid refractory asthma. Administration of 25 mg of etanercept twice a week for 12 weeks produced improvements in lung function seen as improvements in FEV1, FVC and both morning and evening PEF. There was a marked improvement in asthma control and a 2.5 fold doubling dose increase in methacholine airway hyperresponsiveness. Treatment with etanercept markedly reduced the need for rescue medications as all the subjects completely withdrew from their nebulised salbutamol by the end of the study.
University of Southampton
Babu, Kesavan Suresh
d2596db4-dec1-4093-a53b-c8723233a176
2006
Babu, Kesavan Suresh
d2596db4-dec1-4093-a53b-c8723233a176
Babu, Kesavan Suresh
(2006)
The role of Tumour Necrosis Factor alpha (TNF-a) in asthma.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Allergen challenge induces the proinflammatory cytokines and has been used to study the pathogenic mechanisms in asthma. The study presented in Chapter 3 used a repeated low dose allergen challenge model which is more likely to simulate natural allergen exposure to investigate the effects of allergen on bronchial biopsies from mild allergic asthmatics. Low dose allergen exposure results in up regulation of TNF-α in the bronchial biopsies. This increase was associated with a parallel increase in mast cell numbers suggesting the possible source of TNF-α as the mast cells. This was associated with an associated increase in adhesion molecules ICAM-1 and VCAM-1.
In the ex vivo study on bronchial biopsies of moderately severe asthmatics the results were similar to the low dose allergen exposure where TNF-α levels were increased following exposure to Der p and this was suppressed in the presence of CDP 870- a TNF-α blocking monoclonal antibody. CDP 870 was also able to suppress the levels of IL-8 and adhesion molecules.
Having seen a positive response with CDP 870 we had the opportunity of observing the effects of blocking TNF-α with a soluble fusion protein-p75 receptor (etanercept) on patients with chronic severe corticosteroid refractory asthma. Administration of 25 mg of etanercept twice a week for 12 weeks produced improvements in lung function seen as improvements in FEV1, FVC and both morning and evening PEF. There was a marked improvement in asthma control and a 2.5 fold doubling dose increase in methacholine airway hyperresponsiveness. Treatment with etanercept markedly reduced the need for rescue medications as all the subjects completely withdrew from their nebulised salbutamol by the end of the study.
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Published date: 2006
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Local EPrints ID: 466136
URI: http://eprints.soton.ac.uk/id/eprint/466136
PURE UUID: 3f2181c3-7da2-4d44-b2ca-d2e72375501c
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Date deposited: 05 Jul 2022 04:27
Last modified: 16 Mar 2024 20:32
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Author:
Kesavan Suresh Babu
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