Use of cetirizine to investigate non-H1 effects of second-generation antihistamines

Abstract

In addition to their increased potency as H1 blockers and their nonsedating effects, the second-generation antihistamines have other unusual and potentially beneficial properties. Evidence is accumulating from several laboratories that at least one of these agents under investigation, cetirizine, may be effective in inhibiting the late reaction. The Johns Hopkins group showed that during the cutaneous late phase response (LPR), histamine release was not altered by cetirizine, 20 mg, pretreatment. The most dramatic effect of cetirizine was attenuation of inflammatory cell migration into the chamber. Eosinophils, neutrophils, and basophils were reduced by about 75% during hours 6 to 8. It can be concluded that cetirizine influences the LPR by causing a reduction in the inflammatory cell infiltrate. Cetirizine, 10 mg, orally once a day also induced a significant decrease in the wheal and flare skin reactions caused by pollen, histamine, and compound 48/80. Cetirizine inhibited eosinophil recruitment and platelet-activating factor (PAF) in skin chambers 24 hours after pollen challenge. We and others have studied the mechanisms of this effect. The release of eosinophil peroxidase induced by PAF and formyl-methionyleucyl/phenylalanine was not attenuated by cetirizine. At therapeutic concentrations, however, cetirizine has a potent inhibitory action in vitro on eosinophil chemotaxis induced either by formyl-methionyleucyl/phenylalanine or PAF and also on IgE-dependent stimulation of platelets. In a separate study in patients with chronic urticaria, cetirizine markedly reduced both the immediate wheal and flare induced by PAF and the delayed reaction at six hours. These results suggest that cetirizine acts on eosinophil migration to inhibit the late reaction.