title: Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor.
abstract: BACKGROUND
  Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors.
  
  
  OBJECTIVE
  To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells.
  
  
  METHODS
  Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 μmol/L) and substance P (1 μmol/L) with or without pretreatment with RUP (2.5 and 25 μmol/L), which was added 10 minutes before stimulation. Release of β-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 μmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 μmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 μmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect.
  
  
  CONCLUSIONS
  PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation.
authors.affiliation: Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, Massachusetts; Present address: Department of Internal Medicine, Jacoby Medical Center, New York, New York.
authors.forename: Michail
authors.initials: M
authors.lastname: Alevizos
authors.forename: Anna
authors.initials: A
authors.lastname: Karagkouni
authors.forename: Magdalini
authors.initials: M
authors.lastname: Vasiadi
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Sismanopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Makris
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kalogeromitros
authors.forename: Theoharis C
authors.initials: TC
authors.lastname: Theoharides
mesh_terms: D018926:Anti-Allergic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003533:Cyproheptadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D018926:Anti-Allergic Agents; C508606:CXCL8 protein, human; D016209:Interleukin-8; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; C103639:rupatadine; D003533:Cyproheptadine; D013373:Substance P; D006632:Histamine; D001619:beta-N-Acetylhexosaminidases