The recent finding that an antihistamine administered regularly to 1-2 year
s 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 e
ffect simply due to antagonism of histamine, which may have wider actions i
n the development of airway inflammation than previously suspected, or is i
t a result of the anti-allergic properties exhibited by the second generati
on antihistamines! There are now many in vivo studies which have demonstrat
ed that antihistamines decrease mast/basophil cell mediator release, inflam
matory cell infiltration in allergic disease, and expression of adhesion mo
lecules on epithelial cells. Numerous in vitro studies support these findin
gs, extending the anti-inflammatory properties of antihistamines to decreas
ing eosinophil migration and release of proinflammatory mediators. We have
established primary cultures of epithelial cells from nasal biopsies from s
easonal allergic rhinitics outside the pollen season, and studied the effec
t of 0 to 10(-3)M 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 cy
tokines and adhesion molecules. 10(-9) to 10(-3)M fexofenadine significantl
y inhibited eosinophil-induced increases in the permeability of the epithel
ial cell cultures and the release of IL-8, GM-CSF and sICAM-1. In addition,
10(-6) to 10(-3)M fexofenadine significantly inhibited cytokine-induced eo
sinophil chemotaxis and adhesion of these cells to endothelial cells.