Cetirizine inhibits skin reactions but not mediator release in immediate and developing late-phase allergic cutaneous reactions. A double-blind, placebo-controlled study

Background Recent reports have indicated cetirizine, a potent H-1-receptor antagonist, to possess a number of anti-inflammatory effects, e.g. inhibiti on of mast cell degranulation and inhibition of leucocyte migration and act ivation. Objective The aim of this study was to compare the effects of cetirizine on skin responses and mediator release in intact skin in immediate and develo ping late-phase allergic reactions by microdialysis technique. Methods Cetirizine 10 mg once daily or matching placebo were administered t o 10 atopic subjects for 6 days followed by a 2-week washout in a randomize d, double-blind, placebo-controlled, cross-over trial. Immediate skin test responses to allergen, codeine, and histamine and late-phase reactions to a llergen were assessed. The time course of extracellular levels of inflammat ory mediators in intact skin were monitored by microdialysis techniques usi ng 2 kDa and 3 MDa cut-off fibers, respectively. Results Cetirizine significantly reduced immediate weal and flare reactions to allergen, codeine, and histamine. Injection of allergen, but not buffer controls, induced a significant release of histamine, tryptase, prostaglan din D-2, total protein, and eosinophilic cationic protein. No significant i ncrease of leukotriene B-4 and myeloperoxidase was observed. Cetirizine inh ibited early total protein extravasation by 40%, but this did not reach a s ignificant level. None of the inflammatory mediators were significantly inh ibited by cetirizine. Cetirizine significantly reduced the late-phase skin induration to allergen by approximately 30%. Conclusion Cetirizine potently reduced skin responses in immediate allergic reactions without inhibition of early mediators. These data indicate cetir izine to be a potent H-1-receptor antagonist with no effect on mast cell ac tivation. It did not inhibit any of the late-phase mediators, but it reduce d the late skin reaction. These data suggest that mediators other than thos e actually measured may play a significant role in the clinical late-phase reaction.