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The effects of inflammatory mediators on human nasal secretions

Sukonpongpao, J; (2003) The effects of inflammatory mediators on human nasal secretions. Doctoral thesis , University of London. Green open access

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Abstract

Allergic rhinitis is one of the common allergic diseases. Symptoms of allergic rhinitis are pruritus (itching) of the nose, sneezing, nasal congestion and rhinorrhea. Rhinorrhea is a result of an increase in nasal secretion and is one of the fundamental components of allergic rhinitis. The first aim of this thesis was to quantitatively analyse this parameter of the nasal response following nasal challenge with synthetic inflammatory mediators. In order to quantitatively measure the amount of nasal secretion, a simple and relatively non-traumatic method for collecting the secretion was developed. Insertion of a cotton bud into each nostril proved to be an efficient method for quantitatively analysing an increase in nasal secretion produced following exogenous application of synthetic inflammatory mediators. Secondly, the mechanism by which mediators induced nasal secretion was also examined by analysis of protein content in nasal lavage after mediator administration. An increase in albumin concentration indicated an increase in vascular permeability whereas glandular secretion was evaluated by an increase in lysozyme and lactoferrin (serous cell origin) and fucose for mucous glycoprotein secretion (mucous cell origin). This thesis presents an investigation on the secretory activity of human nasal mucosa and the source of the secretion induced by increasing concentrations of methacholine, histamine and bradykinin in normal human subjects, and substance P in atopic and normal subjects. An increase in nasal secretion was observed following nasal challenge with methacholine, histamine and bradykinin. Methacholine- and histamine-induced nasal secretion was a mixture of both vascular and glandular proteins while bradykinin-induced nasal secretion contained protein of vascular origin. The antihistamine, cetirizine, and the bradykinin B2 receptor antagonist, Hoe 140, inhibited histamine- and bradykinin-induced increases in nasal secretion of albumin, respectively. Cetirizine had no effect on histamine-induced glandular secretion. Challenge of one nostril with 1000 lig histamine induced reflex albumin secretion in the opposite, non-challenged nostril. This indicated that histamine may induce neuronal reflexes in normal subjects but a high concentration was needed. The effects of the neuropeptide, substance P, were examined in normal and atopic subjects. Substance P induced a vascular response but not a glandular response. Atopic subjects produced greater responses, albumin release and facial cutaneous blood flow, than in normal subjects.

Type: Thesis (Doctoral)
Title: The effects of inflammatory mediators on human nasal secretions
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: http://discovery.ucl.ac.uk/id/eprint/1514482
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