Rupatadine inhibits proinflammatory mediator secretion from human mast cells triggered by different stimuli

Int Arch Allergy Immunol. 2010;151(1):38-45. doi: 10.1159/000232569. Epub 2009 Aug 6.


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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Anti-Idiotypic / pharmacology
  • Cell Line, Tumor
  • Cells, Cultured
  • Cyproheptadine / analogs & derivatives*
  • Cyproheptadine / pharmacology
  • Cytokines / drug effects*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Histamine / biosynthesis*
  • Histamine / immunology
  • Histamine H1 Antagonists / pharmacology*
  • Humans
  • Interleukin-1 / pharmacology
  • Interleukin-4 / pharmacology
  • Interleukin-6 / pharmacology
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Stem Cell Factor / pharmacology
  • Substance P / pharmacology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / immunology
  • Vascular Endothelial Growth Factor A / metabolism


  • Antibodies, Anti-Idiotypic
  • Cytokines
  • Histamine H1 Antagonists
  • IL4 protein, human
  • IL6 protein, human
  • Interleukin-1
  • Interleukin-6
  • Stem Cell Factor
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • anti-IgE antibodies
  • Interleukin-4
  • rupatadine
  • Cyproheptadine
  • Substance P
  • Histamine