title: Verapamil modulates interleukin-5 and interleukin-6 secretion in organotypic human sinonasal polyp explants.
abstract: BACKGROUND
  Verapamil is an L-type calcium channel blocker (CCB) that has been shown to have immunomodulatory properties in a variety of tissues. The goal of this study was determine whether verapamil is capable of regulating cytokine secretion in sinonasal polyps and to compare this effect to dexamethasone, an established immunosuppressive corticosteroid.
  
  
  METHODS
  This was an institutional review board (IRB)-approved study in sinonasal polyp explants derived from 8 patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Polyps were incubated with dexamethasone or verapamil for 24 hours followed by an additional 24 hours with Staphylococcal enterotoxin B (SEB). Concentrations of secreted cytokines over each exposure period were determined by enzyme-linked immunosorbent assay (ELISA) and are expressed as a percent. Results were compared using a 2-tailed Student t test.
  
  
  RESULTS
  The percent of SEB-stimulated interleukin-5 (IL-5) secretion (mean ± standard deviation [SD], 339.94% ± 315.48%) between the second and first treatment periods was significantly reduced following exposure to dexamethasone (74.08% ± 26.77%, p < 0.05) and verapamil (119.99% ± 69.32%, p < 0.05). The percent of SEB-stimulated IL-6 secretion (217.53% ± 89.51%) was also significantly reduced following exposure to verapamil (148.82% ± 79.15%, p < 0.05) but not dexamethasone (148.86% ± 145.24%). Finally, the percent of SEB-stimulated thymic stromal lymphopoietin (TSLP) secretion (37.86% ± 18.88%) demonstrated a nonsignificant trend toward reduction with both dexamethasone (31.15% ± 35.28%) and verapamil (20.14% ± 12.10%).
  
  
  CONCLUSIONS
  Although the mechanism has yet to be fully understood, L-type CCBs are capable of reducing inflammation in multiple tissues. Verapamil was specifically found to reduce airway goblet cell hyperplasia and eosinophilic infiltration in a murine asthma model. Our data support these findings suggesting that verapamil can modulate T-helper cell type 2 (Th2)-associated cytokine secretion in sinonasal polyp explants. This data points to a possible therapeutic role for CCBs in the management of CRSwNP.
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Bleier
authors.forename: Armine
authors.initials: A
authors.lastname: Kocharyan
authors.forename: Amy
authors.initials: A
authors.lastname: Singleton
authors.forename: Xue
authors.initials: X
authors.lastname: Han
mesh_terms: D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D002908:Chronic Disease; D003907:Dexamethasone / Q000494:pharmacology; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D007166:Immunosuppressive Agents / Q000494:pharmacology; D015848:Interleukin-5 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009298:Nasal Polyps / Q000188:drug therapy* / Q000276:immunology; D009924:Organ Culture Techniques; D010256:Paranasal Sinuses / Q000187:drug effects* / Q000276:immunology; D012220:Rhinitis / Q000188:drug therapy* / Q000276:immunology*; D012852:Sinusitis / Q000188:drug therapy* / Q000276:immunology; D014700:Verapamil / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D004768:Enterotoxins; D007166:Immunosuppressive Agents; D015848:Interleukin-5; D015850:Interleukin-6; C031818:enterotoxin B, staphylococcal; D003907:Dexamethasone; D014700:Verapamil
keywords: calcium channel blocker; chronic rhinosinusitis; explant; nasal polyps; verapamil