Effect of cetirizine on mast cell-mediator release and cellular traffic during the cutaneous late-phase reaction

A new H 1 antihistamine, cetirizine, was studied to determine its effects on mediators and cellular infiltration during the cutaneous late-phase response (LPR). Ten ragweed-allergic subjects, who had previously demonstrated a cutaneous LPR, were examined in a double-blind, crossover study. Either cetirizine, 20 mg, or placebo was administered orally once daily for 2 days before and the morning of placement of a skin chamber overlying an unroofed heat/suction-induced blister to which was added antigen or buffer. Skin test erythema was significantly reduced by cetirizine at 15 minutes, 2 hours, and 4 hours by 56%, 40%, and 39%, respectively (all, p ≤ 0.01), but by 6 and at 8 hours, the cutaneous erythema was not significantly lessened. Histamine release was not altered by cetirizine treatment, but prostaglandin D 2 (PGD 2) production, which peaked at 3 to 5 hours, was clearly reduced by cetirizine treatment, being lower at all time points during the reaction; this was significant by analysis of variance ( p ≤ 0.04). The inhibition was most marked during the fifth hour of the reaction when there was a 50% suppression of the PGD 2 level by cetirizine (0.193 ng/ml to 0.075 ng/ml [ p ≤ 0.03]). The most dramatic effect of cetirizine was attenuation of the inflammatory cell migration into the chamber. Eosinophil infiltration was decreased by about 75% during hours 6, 7, and 8 ( p < 0.04), whereas the number of neutrophils was reduced by the same magnitude at the same times ( p ≤ 0.04). Basophils appeared to enter the chamber together with the eosinophils and were decreased by 64% during hours 6 through 8, but not significantly due to small numbers. We conclude that cetirizine influences the pathogenesis of the LPR by causing a significant reduction in both the inflammatory cell infiltrate and PGD 2 production. These effects apparently are not related to its anti-H 1 activity.