The University of Southampton
University of Southampton Institutional Repository

The role of Tumour Necrosis Factor alpha (TNF-a) in asthma

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
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.

Text
1043888.pdf - Version of Record
Available under License University of Southampton Thesis Licence.
Download (3MB)

More information

Published date: 2006

Identifiers

Local EPrints ID: 466136
URI: http://eprints.soton.ac.uk/id/eprint/466136
PURE UUID: 3f2181c3-7da2-4d44-b2ca-d2e72375501c

Catalogue record

Date deposited: 05 Jul 2022 04:27
Last modified: 16 Mar 2024 20:32

Export record

Contributors

Author: Kesavan Suresh Babu

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×