To increase understanding of the effect of H1
antihistamines on the immediate response to nasal challenge with
antigen, we performed two double blind, placebo-controlled, crossover studies using
cetirizine and
terfenadine. The subjects underwent nasal challenge with
antigen after
premedication with either
cetirizine (20 mg QD for two days, n = 10),
terfenadine (60 mg BID for 1 week, n = 12), or placebo for equivalent periods of time. We monitored the response to challenge by counting the number of sneezes and by measuring the levels of inflammatory substances in recovered nasal lavages. Compared with placebo, both
antihistamines significantly reduced
sneezing and the levels of recovered
albumin and
TAME esterase activity, suggesting that both reduced the expected increase in vascular permeability. With
cetirizine, there was also a reduction in the levels of
LTC4 (not measured in
terfenadine studies) but not in those of recovered
histamine and
prostaglandin D2. These data suggest that
cetirizine did not affect mast cell mediator release, that histamine release is due to the direct action of
antigen stimulation and that
leukotrienes are generated by cells in addition to mast cells. With
terfenadine, there were significant reductions in the levels of
histamine and
kinins (not measured in
cetirizine study) seen after nasal challenge with
antigen. The reduction in
kinins most likely reflects alteration in vascular permeability, whereas the effect on
histamine presumably reflects inhibition of mast cell activation. When combined, these experiments demonstrate effects of H1
antihistamines on histamine release beyond those usually described, as well as differences between drugs within a single classification.