icatibant and Rhinitis--Allergic--Seasonal

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

Topics: Adult; Aerosols; Antigens; Bradykinin; Bradykinin Receptor Antagonists; Bronchial Hyperreactivity; Cross-Over Studies; Eosinophilia; Humans; Kinins; Middle Aged; Nasal Cavity; Nasal Provocation Tests; Rhinitis; Rhinitis, Allergic, Seasonal; Time Factors

We evaluated roles of kinins in allergen-induced nasal blockage and sneezing, and development of nasal hyperresponsiveness to leukotriene D4 in a Japanese cedar pollen-induced allergic rhinitis model of guinea pigs. Sensitised guinea pigs were repeatedly challenged by pollen inhalation once every week. Neither a bradykinin B1 receptor antagonist, des-Arg9-[Leu8]bradykinin nor a bradykinin B2 receptor antagonist, icatibant suppressed allergen-induced sneezing and nasal blockage. However, development of nasal hyperresponsiveness to leukotriene D4 was significantly suppressed by them. The amount of bradykinin in nasal cavity lavage fluid was immediately increased after the challenge. In non-sensitised animals, hyperresponsiveness to leukotriene D4 was developed by a bradykinin B2 receptor agonist, bradykinin, but not by a bradykinin B1 receptor agonist, des-Arg10-kallidin, while in the sensitised-challenged animal, both agonists developed hyperresponsiveness. In conclusion, the nasal hyperresponsiveness appeared to be induced by kinins produced in response to the antigen challenge through activation of not only bradykinin B2 but also B1 receptors.

Topics: Airway Resistance; Allergens; Animals; Bradykinin; Bradykinin B1 Receptor Antagonists; Bradykinin B2 Receptor Antagonists; Disease Models, Animal; Guinea Pigs; Kallidin; Kinins; Leukotriene D4; Male; Nasal Lavage Fluid; Pollen; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Rhinitis, Allergic, Seasonal; Time Factors

In subjects with allergic rhinitis to house-dust mite (HDM), antigen challenge produced a significant increase in nasal blockage but had no effect on nasal vascular permeability. The B2 kinin receptor antagonist, [D-Arg0,Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140), 200 micrograms administered by intranasal aerosol 2 min prior to challenge with HDM, 500 u significantly reduced nasal blockage induced by the antigen challenge. The data are compatible with a role for B2 kinin receptors in the nasal response to challenge with antigen which is responsible for nasal blockage.

Topics: Adult; Aged; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Bradykinin; Bradykinin Receptor Antagonists; Capillary Permeability; Dust; Humans; Middle Aged; Mites; Nose; Receptors, Bradykinin; Rhinitis, Allergic, Seasonal