Effect of H₁ receptor blockade on the early and late response to cutaneous allergen challenge

We investigated whether cutaneous antigen-induced inflammatory cell infiltration and mediator release were modified by H₁ receptor antagonists. Three chemically unrelated antihistamines (cetirizine, promethazine and chlorpheniramine) were tested in three groups of allergic subjects in a double-blind, crossover design. Chamber fluids were collected for 12 hr and histamine release, prostaglandin D₂ production and cellular infiltration were quantified. Cetirizine significantly decreased late leukocyte migration into antigen-challenged chambers: eosinophils by 68% (P < .04), basophils by 64% (P < .04) and neutrophils by 72% (P < .04), whereas mononuclear cells were not significantly affected. No alteration in the numbers of peripheral blood leukocytes or eosinophils occurred while on cetirizine treatment, suggesting that the decrease in inflammatory cells during the late phase reaction in the skin is not secondary to alterations in the peripheral leukocyte pool. In contrast, neither promethazine nor chlorpheniramine induced any significant alteration in inflammatory cell infiltration. All three antihistamines caused significant inhibition of the immediate reaction to antigen without any significant alteration in late phase reaction cutaneous reactivity. None of the three antihistamines caused any significant alteration in histamine or prostaglandin D₂ levels. Thus, cetirizine may be an antihistamine uniquely capable of downregulating the late phase reaction inflammatory cell milieu without altering either early or late mediator production. The mechanisms involved and the clinical relevance of these findings remain to be explored.