title: Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human Fc epsilon RI+ cells.
abstract: BACKGROUND
  Loratadine, a novel histamine H1-receptor antagonist, is effective in the treatment of patients with seasonal and perennial rhinitis and some allergic skin disorders. Histamine and other chemical mediators are synthesized and immunologically released by human peripheral blood basophils and tissue mast cells (Fc epsilon RI+ cells).
  
  
  OBJECTIVE
  To evaluate the effects of loratadine and its main metabolite, desethoxylcarbonyl-loratadine (des-loratadine), on the immunological release of preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C4: LTC4 and prostaglandin D2:PGD2) from human Fc epsilon RI+ cells.
  
  
  METHODS
  Human Fc epsilon RI+ cells purified from peripheral blood and from skin (HSMC) and lung tissue (HLMC) were preincubated with loratadine and des-loratadine before immunological challenge with Der p 1 antigen or anti-Fc epsilon RI. The release of preformed mediators (histamine and tryptase) and de novo synthesized eicosanoids was evaluated in the supernatants of human Fc epsilon RI+ cells.
  
  
  RESULTS
  Preincubation (15 min, 37 degrees C) of purified (36-74%) basophils with loratadine (3 x 10(-6)-10(-4)M) and des-loratadine before Der p 1 antigen or anti-Fc epsilon RI challenge concentration-dependently (5-40%) inhibited the release of histamine and LTC4. Loratadine (3 x 10(-6)-10(-4)M) and des-loratadine also inhibited (10-40%) histamine, LTC4, and PGD2 release from purified HLMC (16-68%) activated by anti-Fc epsilon RI. Loratadine (3 x 10(-6)-10(-4)M) and des-loratadine caused concentration-dependent inhibition (10-40%) of histamine, tryptase, LTC4, and PGD2 release from purified HSMC (24-72%) immunologically challenged with anti-Fc epsilon RI.
  
  
  CONCLUSIONS
  These results indicate that loratadine and its main metabolite have anti-inflammatory activity by inhibiting the release of preformed and de novo synthesized mediators from human Fc epsilon RI+ cells.
authors.affiliation: Division of Clinical Immunology and Allergy, University of Naples Federico II School of Medicine, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Genovese
authors.forename: V
authors.initials: V
authors.lastname: Patella
authors.forename: G
authors.initials: G
authors.lastname: De Crescenzo
authors.forename: A
authors.initials: A
authors.lastname: De Paulis
authors.forename: G
authors.initials: G
authors.lastname: Spadaro
authors.forename: G
authors.initials: G
authors.lastname: Marone
mesh_terms: D000328:Adult; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism*; D053818:Chymases; D006634:Histamine H1 Antagonists / Q000627:therapeutic use*; D006636:Histamine Release; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D017997:Leukotriene C4 / Q000096:biosynthesis; D017336:Loratadine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000276:immunology; D015230:Prostaglandin D2 / Q000096:biosynthesis; D017455:Receptors, IgE / Q000276:immunology*; D012697:Serine Endopeptidases / Q000378:metabolism; D012867:Skin / Q000276:immunology; D053802:Tryptases
chemical_list: D006634:Histamine H1 Antagonists; D017455:Receptors, IgE; C086094:des(ethoxycarbonyl)loratadine; D017997:Leukotriene C4; D017336:Loratadine; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D015230:Prostaglandin D2