Effect of cetirizine on mast cell-mediator release and cellular traffic during the cutaneous late-phase reaction.
A new H1 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 less than or equal to 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 D2 (PGD2) 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 less than or equal to 0.04). The inhibition was most marked during the fifth hour of the reaction when there was a 50% suppression of the PGD2 level by cetirizine (0.193 ng/ml to 0.075 ng/ml [p less than or equal to 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 less than or equal to 0.04), whereas the number of neutrophils was reduced by the same magnitude at the same times (p less than or equal to 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
Charlesworth
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EN
Department of Medicine, Johns Hopkins University School of Medicine, Good Samaritan Hospital, Baltimore, Md 21239.
Kagey-Sobotka
A
A
Norman
P S
PS
Lichtenstein
L M
LM
D000293:Adolescent; D000328:Adult; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D017332:Cetirizine; D004311:Double-Blind Method; D005260:Female; D006098:Granulocytes / Q000187:drug effects*; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D006919:Hydroxyzine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006968:Hypersensitivity, Delayed / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D011897:Random Allocation; D012882:Skin Tests
D006919:Hydroxyzine; D015230:Prostaglandin D2; D017332:Cetirizine