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

Abstract

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).

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.

• Authors: L Michel, M Murrieta-Aguttes, F Jean-Louis, D Levy, L Dubertret
• Journal: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology (Ann Allergy Asthma Immunol) Vol. 85 Issue 1 Pg. 64-9 (Jul 2000) ISSN: 1081-1206 [Print] United States
• PMID: 10923607 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Benzimidazoles
• Histamine H1 Antagonists
• Leukotrienes
• mizolastine
• Histamine

Topics

• Adolescent
• Adult
• Allergens (immunology)
• Antibody Formation
• Benzimidazoles (analysis, blood, pharmacology)
• Blister (metabolism)
• Cell Adhesion
• Cross-Over Studies
• Double-Blind Method
• Exudates and Transudates (chemistry)
• Female
• Histamine (immunology)
• Histamine H1 Antagonists (pharmacology)
• Humans
• Immunity, Cellular
• Inflammation (pathology)
• Leukocyte Count
• Leukotrienes (metabolism)
• Male
• Models, Immunological
• Pollen (immunology)
• Skin (immunology)