title: Chronic urticaria serum induces histamine release, leukotriene production, and basophil CD63 surface expression--inhibitory effects ofanti-inflammatory drugs.
abstract: BACKGROUND
  A role of potential histamine-releasing autoantibodies against the high-affinity IgE receptor on the surface of basophils and mast cells is discussed in the pathogenesis of chronic urticaria. This so-called autoimmune urticaria may be diagnosed by a positive intracutaneous autologous serum skin test, which is found in about 30% of patients with chronic urticaria.
  
  
  OBJECTIVE
  Our purpose was, first, to compare the effect of complement-inactivated sera of 20 patients with chronic urticaria and positive autologous serum skin tests, 20 patients with chronic urticaria and negative skin tests, and 20 control subjects without chronic urticaria (10 atopic and 10 nonatopic subjects) and, second, to analyze the effect of anti-inflammatory drugs on the serum activity.
  
  
  METHODS
  The following assay systems were used: release of histamine in whole blood samples, surface expression of the activation marker CD63 on basophils, and sulfidoleukotriene de novo production in leukocyte suspensions. Whole blood, basophils, and leukocyte suspensions were obtained from a nonatopic and an atopic donor.
  
  
  RESULTS
  Sera of patients with autologous serum skin test positive chronic urticaria resulted not only in significantly increased histamine release compared with skin test-negative chronic urticaria sera but also in a significant higher induction of basophil CD63 surface expression and sulfidoleukotriene de novo production. However, serum activity was neither characteristic for chronic urticaria nor for chronic urticaria with a positive autologous serum skin test. Preincubation with dapsone, chloroquine, and lidocaine dose dependently resulted in a significant reduction of all histamine release, CD63 expression, and sulfidoleukotriene production. In addition, mizolastine was able to inhibit serum-induced sulfidoleukotriene production.
  
  
  CONCLUSIONS
  Further studies investigating the in vivo effect of these drugs will have to clarify their role in the management of the subset of patients with chronic urticaria demonstrating serum-induced inflammatory effects.
authors.affiliation: Department of Dermatology, Hannover Medical University, Hannover, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Wedi
authors.forename: V
authors.initials: V
authors.lastname: Novacovic
authors.forename: M
authors.initials: M
authors.lastname: Koerner
authors.forename: A
authors.initials: A
authors.lastname: Kapp
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000096:biosynthesis* / Q000494:pharmacology; D000954:Antigens, Surface / Q000096:biosynthesis / Q000187:drug effects; D001491:Basophils / Q000187:drug effects / Q000378:metabolism*; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D015289:Leukotrienes / Q000378:metabolism*; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis* / Q000494:pharmacology; D060149:Tetraspanin 30; D014581:Urticaria / Q000097:blood*
chemical_list: D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D000954:Antigens, Surface; C554586:CD63 protein, human; D015289:Leukotrienes; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D002738:Chloroquine; D008012:Lidocaine