Role of kinins in seasonal allergic rhinitis: icatibant, a bradykinin B2 receptor antagonist, abolishes the hyperresponsiveness and nasal eosinophilia induced by antigen.
BACKGROUND
Icatibant, a bradykinin B(2) receptor antagonist, inhibits the reduction in nasal patency after challenge with house dust mite antigen in sensitive subjects and abolishes the nasal hyperresponsiveness induced by platelet-activating factor in nonatopic subjects.


OBJECTIVE
We sought to investigate the effect of icatibant on the response to nasal antigen challenge in subjects with seasonal allergic rhinitis.


METHODS
Patients allergic to grass pollen antigen (n = 9-13) were included in a double-blind, randomized-block, placebo-controlled, crossover study outside the pollen season. Subjects first received an intranasal spray of icatibant (200 microg per nostril) or a saline control. Subjects were then challenged with antigen or diluent (control), and their responses were monitored by using acoustic rhinometry. Six hours later, nasal lavage fluid was collected and quantified for inflammatory cells and various inflammatory mediators (kinin, eosinophil cationic protein, IL-5, and IL-8). At 24 hours, the response of the nasal airways to 200 microg of histamine was assessed, and a further nasal lavage was carried out.


RESULTS
Antigen challenge caused a significant increase in nasal obstruction and albumin extravasation, which was not affected by icatibant. Nasal hyperresponsiveness to histamine was present 24 hours after antigen and was abolished by pretreatment with icatibant. Icatibant also reduced the antigen-induced increase in eosinophils, eosinophil cationic protein, kinin, and IL-8 in nasal lavage fluid.


CONCLUSIONS
Pretreatment with icatibant does not affect the acute inflammatory response in seasonal allergic rhinitis. However, our results imply the involvement of kinins and the bradykinin B(2) receptor in the development of antigen-induced hyperresponsiveness and the associated eosinophilia in the human nasal airway.
Turner
P
P
Department of Pharmacology, University College London, London, United Kingdom.
Dear
J
J
Scadding
G
G
Foreman
J C
JC
D000328:Adult; D000336:Aerosols / Q000008:administration & dosage; D000941:Antigens / Q000009:adverse effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D016535:Bronchial Hyperreactivity / Q000517:prevention & control; D018592:Cross-Over Studies; D004802:Eosinophilia / Q000139:chemically induced / Q000276:immunology; D006801:Humans; D007705:Kinins / Q000502:physiology*; D008875:Middle Aged; D009296:Nasal Cavity / Q000166:cytology; D009299:Nasal Provocation Tests; D012220:Rhinitis / Q000139:chemically induced; D006255:Rhinitis, Allergic, Seasonal / Q000503:physiopathology*; D013997:Time Factors
D000336:Aerosols; D000941:Antigens; D065168:Bradykinin Receptor Antagonists; D007705:Kinins; C065679:icatibant; D001920:Bradykinin