In vivo effects of cetirizine on cutaneous reactivity and eosinophil migration induced by platelet-activating factor (PAF-acether) in man.
The aim of the study was to determine the effect of cetirizine, a new potent H1 antihistamine, on acute cutaneous inflammatory response and eosinophil accumulation induced in vivo by platelet-activating-factor (PAF-acether) and allergen. In a double-blind, crossover study, seven subjects allergic to grass pollen and three nonallergic control subjects received orally either cetirizine, 20 mg/day, or placebo for 4 days. On day 4, the subjects were skin tested with grass pollen and PAF-acether (400 and 40 ng per site). After the challenge, an evaluation of time-course cutaneous eosinophil infiltrations by a skin window technique was performed. Cetirizine pretreatment reduced skin wheal and erythema elicited by allergen and PAF, 400 and 40 ng, by 74.6% (p less than 0.001), 53.9% (p less than 0.001), and 47% (p less than 0.01), respectively. Skin reactivity induced by PAF-acether was also significantly reduced by cetirizine in nonallergic subjects. Cetirizine reduced at hour 24 eosinophil infiltrations induced by allergen and PAF, 400 and 40 ng, by 63% (p less than 0.001), 58.5% (p less than 0.001), and 57.8% (p less than 0.01), respectively. This inhibitory effect of cetirizine on allergen and PAF-induced eosinophil infiltration was already effective 2 hours after the challenge. PAF induced a nonsignificant eosinophil influx in all nonallergic subjects. In conclusion, cetirizine inhibited both the immediate cutaneous response and the eosinophil influx induced by allergen and by a potent eosinophil chemotactic factor, such as PAF-acether. Therefore, cetirizine, besides its anti-H1 effect, has the potential to modulate the allergic inflammatory response.
Fadel
R
R
Unité d'Emmuno-Allergie, Institut Pasteur, Paris, France.
David
B
B
Herpin-Richard
N
N
Borgnon
A
A
Rassemont
R
R
Rihoux
J P
JP
D000328:Adult; D017332:Cetirizine; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D006919:Hydroxyzine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects*; D012882:Skin Tests
D006634:Histamine H1 Antagonists; D010972:Platelet Activating Factor; D006919:Hydroxyzine; D017332:Cetirizine