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 antiallergic drug proven to be effective and safe in the treatment of allergic rhinitis and urticaria.


OBJECTIVE
To quantitatively explore the time course of mediator release and 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 placebo once daily in the first 4-day period and, after a 3-week washout period, vice-versa in the crossover period. On day 4 of each period, a non-invasive in vivo skin chamber technique was used to determine the alteration of vascular permeability, mast cell mediator release, the release of soluble intercellular adhesion molecule -1(sICAM-1) in skin sites challenged with exogenous 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 fluids 2 hours after initiation of the allergic reaction and during the following 6 hours. Both exogenous histamine and allergen induced significant vasodilatation, which was sustained during the 8-hour challenge, as indicated by the accumulation of protein in the chamber fluids. Likewise, both histamine and allergen induced the release of significant amounts of ICAM-1 throughout the 8-hour period. Mizolastine significantly inhibited the histamine- and allergen-induced extravasation (after 2 hours, P = .003; after 8 hours, P = .009; after 2 hours, P = .044; after 8 hours, P = .003 respectively) and the histamine- and allergen-induced--ICAM-1 release (after 2 hours, P = .004; after 8 hours, P = .05; after 2 hours, P = .03 respectively).


CONCLUSIONS
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.
Institut de Recherche Sur La Peau, INSERM U532, Hôpital Saint Louis, Paris, France.
L
L
Michel
M
M
Murrieta-Aguttes
F
F
Jean-Louis
D
D
Levy
L
L
Dubertret
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D000917:Antibody Formation; D001562:Benzimidazoles / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D001768:Blister / Q000378:metabolism; D002448:Cell Adhesion; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005122:Exudates and Transudates / Q000737:chemistry; D005260:Female; D006632:Histamine / Q000276:immunology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D007249:Inflammation / Q000473:pathology; D007958:Leukocyte Count; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D018448:Models, Immunological; D011058:Pollen / Q000276:immunology*; D012867:Skin / Q000276:immunology*
D000485:Allergens; D001562:Benzimidazoles; D006634:Histamine H1 Antagonists; D015289:Leukotrienes; C076170:mizolastine; D006632:Histamine