title: Cetirizine inhibits skin reactions but not mediator release in immediate and developing late-phase allergic cutaneous reactions. A double-blind, placebo-controlled study.
abstract: BACKGROUND
  Recent reports have indicated cetirizine, a potent H(1)-receptor antagonist, to possess a number of anti-inflammatory effects, e.g. inhibition of mast cell degranulation and inhibition of leucocyte migration and activation.
  
  
  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 developing late-phase allergic reactions by microdialysis technique.
  
  
  METHODS
  Cetirizine 10 mg once daily or matching placebo were administered to 10 atopic subjects for 6 days followed by a 2-week washout in a randomized, double-blind, placebo-controlled, cross-over trial. Immediate skin test responses to allergen, codeine, and histamine and late-phase reactions to allergen were assessed. The time course of extracellular levels of inflammatory mediators in intact skin were monitored by microdialysis techniques using 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, prostaglandin D(2), total protein, and eosinophilic cationic protein. No significant increase of leukotriene B(4) and myeloperoxidase was observed. Cetirizine inhibited early total protein extravasation by 40%, but this did not reach a significant level. None of the inflammatory mediators were significantly inhibited by cetirizine. Cetirizine significantly reduced the late-phase skin induration to allergen by approximately 30%.
  
  
  CONCLUSIONS
  Cetirizine potently reduced skin responses in immediate allergic reactions without inhibition of early mediators. These data indicate cetirizine to be a potent H1-receptor antagonist with no effect on mast cell activation. It did not inhibit any of the late-phase mediators, but it reduced the late skin reaction. These data suggest that mediators other than those actually measured may play a significant role in the clinical late-phase reaction.
authors.affiliation: The Allergy Unit, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: P N
authors.initials: PN
authors.lastname: Nielsen
authors.forename: P S
authors.initials: PS
authors.lastname: Skov
authors.forename: L K
authors.initials: LK
authors.lastname: Poulsen
authors.forename: M
authors.initials: M
authors.lastname: Schmelz
authors.forename: L J
authors.initials: LJ
authors.lastname: Petersen
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects; D000996:Antitussive Agents / Q000008:administration & dosage / Q000009:adverse effects; D017332:Cetirizine / Q000494:pharmacology*; D003061:Codeine / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000517:prevention & control*; D004804:Eosinophils / Q000187:drug effects; D005260:Female; D006632:Histamine / Q000008:administration & dosage / Q000009:adverse effects; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced*; D006969:Hypersensitivity, Immediate / Q000139:chemically induced*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D015230:Prostaglandin D2 / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000503:physiopathology*; D012882:Skin Tests; D013997:Time Factors
chemical_list: D000485:Allergens; D000996:Antitussive Agents; D006634:Histamine H1 Antagonists; D018836:Inflammation Mediators; D006632:Histamine; D015230:Prostaglandin D2; D003061:Codeine; D017332:Cetirizine