Effect of H1 receptor blockade on the early and late response to cutaneous allergen challenge.
We investigated whether cutaneous antigen-induced inflammatory cell infiltration and mediator release were modified by H1 receptor antagonists. Three chemically unrelated antihistamines (cetirizine, promethazine and chlorpheniramine) were tested in three groups of allergic subjects in a double-blind, crossover design. Chamber fluids were collected for 12 hr and histamine release, prostaglandin D2 production and cellular infiltration were quantified. Cetirizine significantly decreased late leukocyte migration into antigen-challenged chambers: eosinophils by 68% (P less than .04), basophils by 64% (P less than .04) and neutrophils by 72% (P less than .04), whereas mononuclear cells were not significantly affected. No alteration in the numbers of peripheral blood leukocytes or eosinophils occurred while on cetirizine treatment, suggesting that the decrease in inflammatory cells during the late phase reaction in the skin is not secondary to alterations in the peripheral leukocyte pool. In contrast, neither promethazine nor chlorpheniramine induced any significant alteration in inflammatory cell infiltration. All three antihistamines caused significant inhibition of the immediate reaction to antigen without any significant alteration in late phase reaction cutaneous reactivity. None of the three antihistamines caused any significant alteration in histamine or prostaglandin D2 levels. Thus, cetirizine may be an antihistamine uniquely capable of downregulating the late phase reaction inflammatory cell milieu without altering either early or late mediator production. The mechanisms involved and the clinical relevance of these findings remain to be explored.
Charlesworth
E N
EN
Johns Hopkins University, Department of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland.
Massey
W A
WA
Kagey-Sobotka
A
A
Norman
P S
PS
Lichtenstein
L M
LM
D000485:Allergens; D001491:Basophils / Q000187:drug effects; D017332:Cetirizine; D002744:Chlorpheniramine / Q000494:pharmacology*; D004311:Double-Blind Method; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006919:Hydroxyzine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects; D011398:Promethazine / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000096:biosynthesis; D012882:Skin Tests; D013997:Time Factors
D000485:Allergens; D006634:Histamine H1 Antagonists; D006919:Hydroxyzine; D002744:Chlorpheniramine; D011398:Promethazine; D015230:Prostaglandin D2; D017332:Cetirizine