Anti-allergic properties of antihistamines in humans

Abstract

Summary The recent finding that an antihistamine administered regularly to 1–2 years old children with atopic dermatitis, prevented the subsequent development of asthma in those allergic to grass pollen or house dust mite has focused attention on the properties of this class of therapeutic agents. Is this effect simply due to antagonism of histamine, which may have wider actions in the development of airway inflammation than previously suspected, or is it a result of the anti-allergic properties exhibited by the second generation antihistamines? There are now many in vivo studies which have demonstrated that antihistamines decrease mast/basophil cell mediator release, inflammatory cell infiltration in allergic disease, and expression of adhesion molecules on epithelial cells. Numerous in vitro studies support these findings, extending the anti-inflammatory properties of antihistamines to decreasing eosinophil migration and release of pro-inflammatory mediators. We have established primary cultures of epithelial cells from nasal biopsies from seasonal allergic rhinitics outside the pollen season, and studied the effect of 0 to 10−3M fexofenadine, the main active metabolite of terfenadine, on activated eosinophil-induced changes in electrical resistance (a measure of permeability of epithelial cultures) and release of pro-inflammatory cytokines and adhesion molecules. 10−9 to 10−3M fexofenadine significantly inhibited eosinophil-induced increases in the permeability of the epithelial cell cultures and the release of IL-8, GM-CSF and sICAM-1. In addition, 10−6 to 10−3M fexofenadine significantly inhibited cytokine-induced eosinophil chemotaxis and adhesion of these cells to endothelial cells.