Primary human sinonasal epithelial cell culture model for topical drug delivery in patients with chronic rhinosinusitis with nasal polyposis

J Pharm Pharmacol. 2012 Mar;64(3):449-56. doi: 10.1111/j.2042-7158.2011.01409.x. Epub 2011 Nov 13.

Abstract

Objectives: The primary human sinonasal epithelial cell culture (HSNEC) allows for in-vitro modelling of mucosal responses to topical therapy. Cultures grown from healthy donors may underestimate changes in individuals with chronic sinonasal disease thereby yielding inaccurate results with respect to this large patient population. The purpose of this study was to analyse HSNECs derived from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) to determine whether expected disease dependent variables salient to topical drug delivery persist in culture.

Methods: Cultures were grown from patients with CRSwNP. Ciliary beat frequency (CBF) (basal and stimulated), permeability (trans and paracellular), inflammatory response, and glucocorticoid dose response were measured and compared with healthy controls.

Key findings: Methylcholine stimulated CBF was greater in CRSwNP versus controls (ΔCBF(60 min) 7.25 ± 1.02 vs 0.89 ± 1.04 Hz, respectively). Paracellular permeability was greater in CRSwNP versus controls (basolateral dextran(120 min) 18.97 ± 3.90 vs 11.31 ± 4.35 µg/ml, respectively). Lipopolysaccharide (0.1 mg/ml) stimulated interleukin-6 (IL-6) and IL-8 secretion was increased in CRSwNP versus controls (IL-6 Δbaseline 1738.72 ± 654.82 vs 1461.61 ± 533.51%, respectively; IL-8 Δbaseline 137.11 ± 0.83 vs 111.27 ± 0.67%, respectively). CRSwNP cultures were more sensitive than controls to dexamethasone (1 µg/ml) dependent IL-6 and IL-8 suppression.

Conclusions: HSNECs derived from patients with CRSwNP retained their primary phenotype with respect to ciliary function, epithelial permeability, irritant induced inflammatory cytokine secretion, and glucocorticoid dose response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Case-Control Studies
  • Cells, Cultured / drug effects
  • Chronic Disease
  • Cilia / drug effects
  • Dexamethasone / therapeutic use*
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Glucocorticoids / therapeutic use*
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Models, Biological
  • Nasal Mucosa / drug effects*
  • Nasal Polyps / drug therapy*
  • Nasal Polyps / genetics
  • Phenotype
  • Rhinitis / drug therapy*
  • Sinusitis / drug therapy*
  • Sinusitis / genetics

Substances

  • Glucocorticoids
  • Interleukin-6
  • Interleukin-8
  • Dexamethasone