Austin, Caroline Elizabeth; (1994) In vivo studies on the actions of platelet-activating factor and kinins in allergic rhinitis. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Platelet-activating factor (PAF) and kinins have been implicated, among other inflammatory mediators, in the pathophysiology of allergic rhinitis. This thesis describes a human model for quantifying the nasal allergic response, involving rhinomanometry, acoustic rhinometry and nasal lavage techniques, which have been used for examining nasal patency, vascular permeability, mast cell and eosinophil activation. The model was used to investigate the actions of PAF and kinins as putative mediators of allergic rhinitis, in the human nasal airway. Bradykinin caused dose-related increases in nasal blockage and vascular permeability. A B1 agonist had no effect in the nasal airway, but the effects of bradykinin could be inhibited by B2 receptor antagonists. In addition, the effects of bradykinin could also be reduced by prior administration of the H1 receptor antagonist, cetirizine or terfenadine. In patients with perennial allergic rhinitis, antigen challenge resulted in an increase in nasal blockage which could be significantly attenuated by a B2 receptor antagonist, but the antigen had no effect on vascular permeability. PAF induced a non-specific nasal hyperresponsiveness, which was maximal at 6 hours following treatment. It persisted for up to 24 hours and was associated with eosinophil activation in the nasal cavity. In addition, it was found that the oxygen free-radical scavenger, vitamin E, inhibited hyperresponsiveness and eosinophil activation induced by PAF. These studies suggest that PAF may be involved in the nasal hyperresponsiveness characteristic of allergic rhinitis and that bradykinin causes vasodilatation and increases in vascular permeability in the nasal airway. Bradykinin appears to have direct B2 receptor-mediated effects and can possibly also act via a histamine-mediated mechanism. In addition, these studies indicate that the pathophysiology of seasonal and perennial allergic rhinitis may differ.

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