Humoral and cellular responses to histamine and pollen allergen in a skin chamber model: effect of mizolastine

Background: Mizolastine is a new non-sedative antihistamine and antiallergi c drug proven to be effective and safe in the treatment of allergic rhiniti s and urticaria. Objective: To quantitatively explore the time course of mediator release an d cell recruitment during allergen challenge and the effects of mizolastine on the event, using the skin chamber model. Methods: Twelve pollen-sensitive patients (23 +/- 6 years) were included in a double-blind crossover study. Patients received 10 mg mizolastine or pla cebo once daily in the first 4-day period and, after a 3-week washout perio d, vice-versa in the crossover period. On day 4 of each period, a non-invas ive in vivo skin chamber technique was used to determine the alteration of vascular permeability, mast cell mediator release, the release of soluble i ntercellular adhesion molecule -1(sI-CAM-1) in skin sites challenged with e xogenous histamine or grass pollen allergen extract, over an 8-hour period. Results: Challenge with allergen-induced significant mast cell activation, as indicated by the release of histamine, tryptase and LTC4, in chamber flu ids 2 hours after initiation of the allergic reaction and during the follow ing 6 hours. Both exogenous histamine and allergen induced significant vaso dilatation, which was sustained during the 8-hour challenge, as indicated b y the accumulation of protein in the chamber fluids. Likewise, both histami ne and allergen induced the release of significant amounts of ICAM-1 throug hout the 8-hour period. Mizolastine significantly inhibited the histamine a nd allergen-induced extravasation (after 2 hours, P = .003; after 8 hours, P = .009; after 2 hours, P = .044; after 8 hours, P = .003 respectively) an d the histamine- and allergen-induced-ICAM-1 release (after 2 hours, P = .0 04; after 8 hours, P = .05; after 2 hours, P = .03 respectively). Conclusion: Mizolastine strongly inhibited the local response to histamine in this skin chamber model with, of interest, inhibition of the release of the soluble adhesion-molecule ICAM-1.