title: Rupatadine inhibits proinflammatory mediator secretion from human mast cells triggered by different stimuli.
abstract: BACKGROUND
  Mast cells are involved in allergy and inflammation by secreting multiple mediators including histamine, cytokines and platelet-activating factor. Certain histamine 1 receptor antagonists have been reported to inhibit histamine secretion, but the effect on cytokine release from human mast cells triggered by allergic and other stimuli is not well known. We investigated the ability of rupatadine, a potent histamine 1 receptor antagonist that also blocks platelet-activating factor actions, to also inhibit mast cell mediator release.
  
  
  METHODS
  Rupatadine (1-50 microM) was used before stimulation by: (1) interleukin (IL)-1 to induce IL-6 from human leukemic mast cells (HMC-1 cells), (2) substance P for histamine, IL-8 and vascular endothelial growth factor release from LAD2 cells, and (3) IgE/anti-IgE for cytokine release from human cord blood-derived cultured mast cells. Mediators were measured in the supernatant fluid by ELISA or by Milliplex microbead arrays.
  
  
  RESULTS
  Rupatadine (10-50 microM) inhibited IL-6 release (80% at 50 microM) from HMC-1 cells, whether added 10 min or 24 h prior to stimulation. Rupatadine (10-50 microM for 10 min) inhibited IL-8 (80%), vascular endothelial growth factor (73%) and histamine (88%) release from LAD2 cells, as well as IL-6, IL-8, IL-10, IL-13 and tumor necrosis factor release from human cord blood-derived cultured mast cells.
  
  
  CONCLUSIONS
  Rupatadine can inhibit histamine and cytokine secretion from human mast cells in response to allergic, immune and neuropeptide triggers. These actions endow rupatadine with unique properties in treating allergic inflammation, especially perennial rhinitis and idiopathic urticaria.
authors: Molecular Immunopharmacology and Drug Discovery Laboratory, Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts Medical Center, Boston, Mass. 02111, USA.
authors: Magdalini
authors: M
authors: Vasiadi
authors: Dimitris
authors: D
authors: Kalogeromitros
authors: Duraisamy
authors: D
authors: Kempuraj
authors: Anthony
authors: A
authors: Clemons
authors: Bodi
authors: B
authors: Zhang
authors: Caterina
authors: C
authors: Chliva
authors: Michael
authors: M
authors: Makris
authors: Adam
authors: A
authors: Wolfberg
authors: Michael
authors: M
authors: House
authors: Theoharis C
authors: TC
authors: Theoharides
mesh_terms: D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016207:Cytokines / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006632:Histamine / Q000096:biosynthesis* / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D019089:Stem Cell Factor / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism
chemical_list: D000888:Antibodies, Anti-Idiotypic; D016207:Cytokines; D006634:Histamine H1 Antagonists; C508598:IL4 protein, human; C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D019089:Stem Cell Factor; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C026408:anti-IgE antibodies; D015847:Interleukin-4; C103639:rupatadine; D003533:Cyproheptadine; D013373:Substance P; D006632:Histamine